Novel heterocyclic compounds having antibacterial activity: process for their preparation and pharmaceutical compositions containing them

ABSTRACT

The present invention relates to novel oxazolidinone compounds of formula (I), their stereoisomers, their salts and pharmaceutical compositions containing them.  
                 
 
     The present invention also relates to a process for the preparation of the above said novel compounds, their stereoisomers, their salts and pharmaceutical compositions.

FIELD OF THE INVENTION

[0001] The present invention relates to novel oxazolidinone compounds offormula (I), their stereoisomers, their salts and pharmaceuticalcompositions containing them.

[0002] The present invention also relates to a process for thepreparation of the above said novel compounds, their stereoisomers,their salts and pharmaceutical compositions.

BACKGROUND OF THE INVENTION

[0003] Since the discovery of penicillin, pharmaceutical companies haveproduced more than one hundred antibacterial agents to combat a widevariety of bacterial infections. In the past several years, there hasbeen rapid emergence of bacterial resistance to several of theseantibiotics. The multi-drug resistance among these bacterial pathogensmay also be due to mutation leading to more virulent clinicalisolations. The most disturbing milestone has been the acquisition ofresistance to vancomycin, an antibiotic generally regarded as the agentof last resort for serious Gram-positive infections. It is believed thatthe proliferation of multidrug resistant bacteria is brought on by awide spread use, or rather misuse, of existing antibacterials, furtherexacerbated by the use of antibacterials as feed supplements in farmanimals and poultry.

[0004] Bacterial infection is a long-term problem that requiresinnovative new therapeutics. Moreover, in view of the increasing reportsof vancomycin-resistant bacterial isolates and growing problem ofbacterial resistance, there is an urgent need for new molecular entitieseffective against the emerging bacterial organisms. The growing problemof multidrug resistance has intensified the search for new antibiotics.Yet new drugs are difficult to develop and bacterial strains resistantto new drugs may quickly emerge. For example, soon after introduction ofLinezolid (Zyovx™, Pharmacia Upjohn), a representative of a firstentirely new class of antibacterials released into the market over thepast 30 years, clinics reported cases of resistance (Lancet 2001,358(9277): 207-8). Resistant strains have been selected in the lab wherea target site alteration was found to reduce drug binding (Antimicrob.Agents Chemother. 2001, 3(3): 288-294).

[0005] Oxazolidinones, a class of compounds that includes Linezolid,contain an oxazolidinone moiety

[0006] For example, compounds of the generalized structure

[0007] are known in the prior art. In these compounds, a heterocyclicmoiety (Het) is connected to the oxazolidinone moiety through anaromatic nucleus (Ar). Specific examples of oxazolidinone compounds aredisclosed in International publication nos. WO 01/09107, WO 97/27188, WO96/13502 and WO 96/13502. Certain oxazolidinones are believed to beuseful as antibacterials (J. Med. Chem., 1996, 39, 673), antihistaminesand anti allergic agents (EP 291,244), anticonvulsants (DE 3,915,184),as well as for treating cognition disorders, anti psychotics, antiplatelet aggregators, antidepressants, sedatives, hypnotics, and asmonoamine oxidase inhibitors (WO 97/13768).

SUMMARY OF THE INVENTION

[0008] In accordance with one aspect, the invention provides compoundsthat are new oxazolidinone derivatives, or salts thereof, orstereoisomers thereof, the molecules of which include a) a heterocyclicmoiety containing a 5-membered heterocyclic skeleton that is at leastpartially saturated; b) a benzene ring, which may be substituted orunsubstituted; and c) an oxazolidinone moiety, wherein theheterocycliclic moiety is connected to the oxazolidinone moiety throughthe benzene ring. Specific embodiments are described in detail.

[0009] In accordance with others aspects, the invention also provide amethod of using various oxazolidinone compounds, processes for theirpreparation, and pharmaceutical compositions containing such compounds.

DETAILED DESCRIPTION OF THE INVENTION

[0010] The present invention provides a novel oxazolidinone compoundshaving the general formula (I),

[0011] or a salt thereof or a stereoisomer thereof,

[0012] where R¹ is halo, azido, isothiocyano, thioalcohol, —OR⁴, —NHR⁴or —N(R⁴)₂, where R⁴ represents hydrogen atom, or substituted orunsubstituted groups selected from (C₁-C₁₀)alkyl, (C₁-C₁₀)acyl,thio(C₁-C₁₀)acyl, —C(═O)—(C₁-C₁₀)alkoxy, —C(═S)—(C₃-C₈)cycloalkoxy,—C(=O)—(C₂-C₁₀)alkenyloxy, —C(═O)—(C₂-C₁₀)alkenyl, —C(═O)-aryloxy,—C(═S)—C₁-C₁₀)alkoxy, —C(═S)—(C₂-C₁₀)alkenyloxy, —C(═S)-aryloxy,—C(═O)—C(═O)—(C₁-C₁₀)alkyl, —C(═O)—C(═O)-aryl,—C(═O)—C(═O)—(C₁-C₁₀)alkoxy, —C(═O)—C(═O)-aryloxy,—(C═S)—S—(C₁-C₁₀)alkyl, —(C═S)—NH₂, —(C═S)—NH—(C₁-C₁₀)alkyl,—C(═S)—N—((C₁-C₁₀)alkyl)₂, —C(═S)—NH—(C₂-C₁₀)alkenyl,(C═S)—(C═O)—(C₁-C₁₀)alkoxy, —(C═S)—(C═O)-aryloxy,—C(═S)—O—(C═O)—(C₁-C₁₀)alkyl, C(═S)—C(═S)—(C₁-C₁₀)alkyl,—C(═S)—C(═S)-aryl, thiomorpholinyl-C(═S)— or pyrrolidinyl-C(═S)—;

[0013] R² and R³, which may be the same or different, are eachindependently hydrogen, halogen, (C₁-C₁₀)alkyl, halogenated(C₁-C₁₀)alkyl, cyano, nitro, SR^(a), NR^(a), or OR^(a), in which R^(a)is hydrogen, (C₁-C₁₀)alkyl or halogenated (C₁-C₁₀)alkyl;

[0014] is a heterocyclic moiety in which

[0015] is a 5-membered heterocyclic skeleton, Z represents O, S, ═CH,—CH₂ or NR⁶, where R^(b) is hydrogen or a moiety, which may besubstituted or unsubstituted, straight chain or branched, selected fromthe group consisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl,(C₃-C₈)cycloalkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkylamino, amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl,aryloxy, (C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀)alkoxycarbonyl andaryloxycarbonyl;

[0016] Y¹ represents ═O or ═S group and Y² and Y³ independentlyrepresent hydrogen, halogen, cyano, nitro, formyl, hydroxy, amino, ═O,═S group or substituted or unsubstituted groups selected from(C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkoxy C₁-C₁₀alkyl, (C₁-C₁₀)alkylcarbonyl,(C₁-C₁₀)alkoxycarbonyl, arylcarbonyl, carboxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylsulfonyl, (C₁-C₁₀)alkylcarbonyl (C₁-C₁₀)alkyl,arylcarbonylamino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyloxy (C₁-C₁₀)alkyl,amino(C₁-C₁₀)alkyl, mono(C₁-C₁₀)alkylamino, di(C₁-C₁₀)alkylamino,arylamino, (C₁-C₁₀)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl or heterocycloalkyl; Y² and Y³ when presenton adjacent carbon atoms together may also form a substituted orunsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure,optionally containing one or two hetero atoms selected from oxygen,sulfur or nitrogen.

[0017] Suitable groups represented by R⁴ may be selected from hydrogenatom, (C₁-C₁₀)alkyl group such as methyl, ethyl, propyl, butyl and thelike, which may be substituted; (C₁-C₁₀)acyl group of the formula—C(═O)R^(Z) where R^(Z) is hydrogen, (C₁-C₁₀)alkyl, aryl or heteroarylwherein aryl is a group such as phenyl, naphthyl and the like; andheteroaryl is a group such as pyridyl, pyrrolidinyl, piperidinyl,indolyl, furyl and the like; wherein the acyl group is a group such as—C(═O)H, —C(═O)CH₃, —C(═O)CH₂CH₃, —C(═O)(CH₂)₂CH₃, —C(═O)(CH₂)₃CH₃,—C(═O)(CH₂)₄CH₃, —C(═O)(CH₂)₅CH₃, —C(═O)Ph and the like, the acyl groupmay be substituted; thio(C₁-C₁₀)acyl group of the formula —C(═S)R^(Z)where R^(Z) is hydrogen, (C₁-C₁₀)alkyl, aryl or heteroaryl wherein arylis a group such as phenyl, naphthyl and the like; and heteroaryl is agroup such as pyridyl, pyrrolidinyl, piperidinyl, indolyl, furyl and thelike wherein the thioacyl group is a group such as —C(═S)H, —C(═S)CH₃,—C(═S)CH₂CH₃, —C(═S)Ph and the like, the thioacyl group may besubstituted; —C(═O)—(C₁-C₁₀)alkoxy group, containing (C₁-C₁₀)alkyl groupwhich may be linear or branched, such as —C(═O)-methoxy, —C(═O)-ethoxy,—C(═O)-propoxy, —C(═O)-isopropoxy and the like, the—C(═O)—(C₁-C₁₀)alkoxy group may be substituted;—C(═S)-cyclo(C₃-C₈)alkoxy group such as —C(═S)-cyclopropoxy,—C(═S)-cyclobutoxy, —C(═S)-cyclopentoxy, —C(═S)-cyclohexoxy and thelike, the —C(═S)-cyclo(C₃-C₆)alkoxy may be substituted;—C(═O)—(C₂-C₆)alkenyl such as —C(═O)-ethenyl, —C(═O)-propenyl,—C(═O)-butenyl and the like, the —C(═O)—(C₂-C₁₀)alkenyl may besubstituted; —C(═O)—(C₂-C₁₀)alkenyloxy group such as —C(═O)-ethenyloxy,—C(═O)—propenyloxy, —C(═O)-butenyloxy and the like, the—C(═O)—(C₂-C₆)alkenyloxy may be substituted; —C(═O)-aryloxy group suchas —C(═O)-phenoxy, —C(═O)-benzyloxy group and the like, the—C(═O)-aryloxy group may be substituted; —C(═S)—(C₁-C₁₀)alkoxy groupsuch as CH₃O—C(═S)—, C₂H₅O—C(═S)—C₃H₇O—C(═S)—, isopropoxy-C(═S)— and thelike, which may be substituted; —C(═S)—(C2-C10)alkenyloxy group such as—C(═S)-ethenyloxy, —C(═S)—propenyloxy, —C(═S)-butenyloxy and the like,the —C(═S)—(C₂-C₁₀)alkenyloxy group may be substituted; —C(═S)-aryloxygroup such as phenyl-O—C(═S)—, benzyl-O—C(═S)— and the like, which maybe substituted; —C(═O)—C(═O)—(C₁-C₁₀)alkyl group such as—C(═O)—C(═O)methyl, —C(═O)—C(═O)ethyl, —C(═O)—C(═O)propyl,—C(═O)—C(═O)butyl and the like, which may be substituted;—C(═O)—C(═O)-aryl group such as —C(═O)—C(═O)phenyl, —C(═O)—C(═O)naphthyland the like, which may be substituted; —C(═O)—C(═O)—(C₁-C₁₀)alkoxygroup such as —C(═O)—C(═O)methoxy, —C(═O)—C(═O)ethoxy,—C(═O)—C(═O)propyloxy and the like, which may be substituted;—C(═O)—C(═O)-aryloxy group such as —C(═O)—C(═O)phenoxy,—C(═O)—C(═O)benzyloxy, which may be substituted; —(C═S)—S—(C₁-C₁₀)alkylsuch as —(C═S)—S-methyl, —(C═S)—S-ethyl, —(C═S)—S-propyl and the like,which may be substituted; —(C═S)—NH₂; —(C═S)—NH—(C₁-C₁₀)alkyl such as—(C═S)—NH-methyl, —(C═S)—NH-ethyl, —(C═S)—NH-propyl and the like, whichmay be substituted; —C(═S)—N—((C₁-C₁₀)alkyl)₂ such as—C(═S)—N-(methyl)₂, —C(═S)—N-(ethyl)₂, —C(═S)—N-(propyl)₂ and the like,which may be substituted; —C(═S)—NH—(C₂-C₁₀)alkenyl such as—C(═S)—NH-ethenyl, —C(═S)—NH-propenyl, —C(═S)—NH-butenyl and the like,which may be substituted; —(C═S)—(C═O)—(C₁-C₁₀)alkoxy such as—(C═S)—(C═O)-methoxy, —(C═S)—(C═O)-ethoxy, —(C═S)—(C═O)-propoxy and thelike, which may be substituted; —(C═S)—(C═O)-aryloxy such as—(C═S)—(C═O)-phenoxy, —(C═S)—(C═O)-naphthyloxy and the like, which maybe substituted; —C(═S)—O—(C═O)—(C₁-C₁₀)alkyl such as—C(═S)—O—(C═O)-methyl, —C(═S)—O—(C═O)-ethyl, —C(═S)—O—(C═O)-propyl andthe like, which may be substituted; —C(═S)—C(═S)—(C₁-C₁₀)alkyl groupsuch as —C(═S)—C(═S)methyl, —C(═S)—C(═S )ethyl, —C(═S)—C(═S)propyl andthe like, which may be substituted; —C(═S—)—C(═S)aryl group such as—C(═S)—C(═S)phenyl, —C(═S)—C(═S)naphthyl and the like, which may besubstituted; thiomorpholinyl-C(═S)— which may be substituted; orpyrrolidinyl-C(═S)— which may be substituted.

[0018] When the groups represented by R⁴ are substituted, thesubstituents may be selected from halogen atom such as chlorine,fluorine, bromine and iodine; hydroxy, amino, mono(C₁-C₁₀)alkylaminosuch as methylamino, ethylamino, propylamino and the like,di(C₁-C₁₀)alkylamino such as dimethylamino, diethylamino,methylethylamino, dipropylamino, ethylpropylamino and the like, cyano,nitro, (C₁-C₁₀)alkoxy, aryl such as phenyl, naphthyl and the like;hydroxyaryl, pyridyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkoxyaryl or carboxyl and its derivatives such as amides likeCONH₂, CONHMe, CONMe₂, CONHEt, CONEt₂, CONHPh and the like, and esterssuch as COOMe, COOEt and the like.

[0019] Suitable groups represented by R² and R³ may be selected fromhydrogen, halogen atom such as fluorine, chlorine or bromine;(C₁-C10)alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl,iso-butyl, t-butyl, n-pentyl, iso-pentyl, n-hexyl and the like;halo(C₁-C₁₀)alkyl group such as halomethyl, haloethyl, halopropyl,trihalomethyl and the like, wherein the halo group is selected fromfluorine, chlorine, bromine or iodine; cyano, nitro; SR^(a), NR^(a),OR^(a) where R^(a) represents hydrogen or substituted or unsubstituted(C₁-C₁₀)alkyl group such as methyl, ethyl, propyl, isopropyl and thelike; halo(C₁-C₁₀)alkyl such as halomethyl, haloethyl, halopropyl,haloisopropyl and the like, where the halo group is selected from fluro,chloro, bromo or iodo.

[0020] The substituents on R^(a) are selected from hydroxy, halogen,nitro, amino, (C₁-C₁₀)alkoxy, carboxyl or cyano.

[0021] Suitable groups represented by Z may be selected from S, O, ═CHor NR^(b) where R^(b) represents hydrogen or substituted orunsubstituted (C₁-C₁₀)alkyl such as methyl, ethyl, propyl, butyl, pentyland the like, which may be substituted; (C₂-C₁₀)alkenyl such as ethenyl,propenyl, butenyl and the like, which may be substituted;(C₃-C₈)cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl and the like, which may be substituted; hydroxy(C₁-C₁₀)alkylsuch as hydroxymethyl, hydroxyethyl, hydroxypropyl, propyldihydroxy andthe like, which may be substituted; (C₁-C₁₀)alkylhydroxy such asmethylhydroxy, ethylhydroxy, propylhydroxy. propyldihydroxy and thelike, which may be substituted; (C₁-C₁₀)alkylamino such as methylamino,ethylamino, propylamino, butylamino and the like, which may besubstituted, amino(C₁-C₁₀)alkyl such as aminomethyl, aminoethyl,aminopropyl, aminobutyl and the like, which may be substituted;(C₁-C₁₀)alkoxy such as methoxy, propoxy, isopropoxy and the like, whichmay be substituted; aryl group such as phenyl, naphthyl and the like,which may be substituted; aralkyl such as benzyl, phenethyl and thelike, which may be substituted; aryloxy such as phenyloxy, naphthyloxyand the like, which may be substituted; (C₁-C₁₀)alkylcarbonyl such asmethylcarbonyl, ethylcarbonyl, propylcarbonyl and the like, which may besubstituted; arylcarbonyl such as phenylcarbonyl, naphthylcarbonyl andthe like, which may be substituted; (C₁-C₁₀)alkoxycarbonyl such asmethoxycarbonyl, ethoxycarbonyl, propoxycarbonyl and the like, which maybe substituted; or aryloxycarbonyl such as phenyloxycarbonyl,naphthyloxycarbonyl and the like, which may be substituted.

[0022] The substituents on R^(b) are selected from hydroxy, halogen,pyrrolidinyl-C(═S)—, nitro, amino, (C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy,carboxyl, oxo, thiooxo or cyano.

[0023] Y¹ represents ═O or ═S group, Y² and Y³ are selected fromhydrogen, halogen such as fluorine, chlorine, bromine or iodine; cyano,nitro, formyl, hydroxy, amino, ═O, ═S group, substituted orunsubstituted (C₁-C₁₀)alkyl such as methyl, ethyl, n-propyl, isopropyl,n-butyl, iso-butyl, t-butyl and the like; hydroxy(C₁-C₁₀)alkyl such ashydroxymethyl, hydroxyethyl, hydroxypropyl, propyldihydroxy and thelike, which may be substituted; (C₁-C₁₀)alkylhydroxy such as methylhydroxy, ethylhydroxy, propylhydroxy. propyldihydroxy and the like,which may be substituted; (C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl group such asmethoxymethyl, methoxyethyl, ethoxyethyl, ethoxymethyl, methoxypropyl,propoxymethyl, propoxyethyl and the like, which may be substituted;(C₁-C₁₀)alkylcarbonyl group such as methylcarbonyl, ethylcarbonyl andthe like, which may be substituted; arylcarbonyl group such asphenylcarbonyl, naphtylcarbonyl and the like, which may be substituted;(C₁-C₁₀)alkoxycarbonyl group such as methoxycarbonyl, ethoxycarbonyl andthe like, which may be substituted; carboxy(C₁-C₁₀)alkyl such asCH₃—COO, CH₃—CH₂—COO and the like, which may be substituted;(C₁-C₁₀)alkylsulfonyl group such as methylsulfonyl, ethylsulfonyl andthe like, which may be substituted;(C₁-C₁₀)alkylcarbonylamino(C₁-C₁₀)alkyl groups such asmethylcarbonylaminomethyl, ethylcarbonylaminomethyl,methylcarbonylaminoethyl, ethylcarbonylaminoethyl and the like, whichmay be substituted; arylcarbonylamino(C₁-C₁₀)alkyl such asphenylcarbonylaminomethyl, phenylcarbonylaminoethyl,naphtylcarbonylaminomethyl, naphthylcarbonylaminoethyl and the like,which may be substituted; (C₁-C₁₀)alkylcarbonyloxy(C₁-C₁₀)alkyl groupsuch as methylcarbonyloxymethyl, ethylcarbonylxoymethyl,methylcarbonyloxyethyl, propylcarbonyloxymethyl, propylcarbonyloxyethyl,propylcarbonyloxypropyl and the like, which may be substituted;amino(C₁-C₁₀)alkyl such as aminomethyl, aminoethyl, aminopropyl and thelike, which may be substituted; mono(C₁-C₁₀)alkylamino such asmethylamino, ethylamino, propylamino and the like, which may besubstituted; di(C₁-C₁₀)alkylamino sich as dimethylamino, diethylamino,methylethylamino, dipropylamino, ethylpropylamino and the like, whichmay be substituted; arylamino such as phenylamino, benzylamino and thelike, which may be substituted; (C₁-C₁₀)alkoxy group such as methoxy,ethoxy, propoxy, isopropoxy and the like, which may be substituted; arylgroup such as phenyl, naphthyl and the like, which may be substituted;aryloxy group such as phenoxy, naphthyloxy and the like, the aryloxygroup may be substituted; aralkyl such as benzyl, phenethyl,C₆H₅CH₂CH₂CH₂, naphthylmethyl and the like, the aralkyl group may besubstituted; heteroaryl groups such as pyridyl, thienyl, furyl,pyrrolyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, oxadiazolyl,tetrazolyl, benzopyranyl, benzofuranyl and the like, which may besubstituted; heteroaralkyl such as imidazolemethyl, imidazoleethyl,pyridylmethyl, furyl methyl, oxazolemethyl, imidazolyl and the like,which may be substituted; heterocyclyl group such as pyrrolidinyl,piperidinyl, morpholinyl, piperazinyl and the like; heterocycloalkylgroups such as pyrrolidinemethyl, piperidinemethyl, morpholinemethyl,piperazinemethyl and the like, which may be substituted.

[0024] When the groups represented by Y² and Y³ are substituted, thesubstituents may be selected from hydroxy, nitro, cyano, amino,(tert-butyldimethylsilyloxy) TBSO, halogen atom, (C₁-C₁₀)alkyl,(C₁-C₁₀)alkoxy, (C₃-C₈)cycloalkyl, aryl group such as phenyl, naphthyland the like, benzyloxy, acyl group such as formyl, acetyl, and thelike, carboxyl or acyloxy group such as formyloxy, acetyloxy and thelike.

[0025] Suitable cyclic structure formed by Y² and Y³ when present onadjacent carbon atoms which they are attached may be selected fromsubstituted or unsubstituted benzene, pyridine, pyrrolidine, furan,thiophene, morpholine, piperazine, pyrrole and the like. Thesubstituents on the cyclic structure formed by Y² and Y³ are selectedfrom halogen, hydroxyl, amino, cyano, nitro, oxo, thioxo, (C₁-C₁₀)alkylor (C₁-C₁₀)alkoxy, where (C₁-C₁₀)alkyl and (C₁-C₁₀)alkoxy groups are asdefined earlier.

[0026] When the groups R¹, R⁴, R^(b), Y² and Y³ are substituted, theymay be mono- or di- or tri substituted.

[0027] The invention provides separate embodiments of the compounds ofthe invention, which are however not necessarily exclusive of oneanother. In one embodiment, there are provided oxazolidinone derivativesof the structure in accordance with the formula (I).

[0028] Oxazolidinone derivatives of one group of this embodiment havethe structure

[0029] wherein X¹ is oxygen or sulfur.

[0030] Oxazolidinone derivatives of another group of this embodimenthave the structure

[0031] wherein X¹ is oxygen or sulfur.

[0032] Oxazolidinone derivatives of yet another group of this embodimenthave the structure

[0033] wherein X¹ is oxygen or sulfur, and

[0034] is a substituted or unsubstituted 5- or 6-membered aromatic ornon-aromatic cyclic structure optionally having one or two hetero atoms,formed by Y² and Y³.

[0035] Oxazolidinone derivatives of another group of this embodimenthave the structure

[0036] wherein X¹ is oxygen or sulfur.

[0037] Oxazolidinone derivatives of another group of this embodimenthave the structure

[0038] wherein X¹ is oxygen or sulfur.

[0039] In another embodiment, the invention also provides oxazolidinonederivatives that have the structure, in accordance with the compound offormula (I)

[0040] or a salt thereof or a stereoisomer thereof,

[0041] where R^(N) is

[0042] wherein R^(b) is hydrogen or a moiety, which may be substitutedor unsubstituted, straight chain or branched, selected from the groupconsisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, (C₃-C₈)cycloalkyl,(C₁-C₁₀)alkoxy, aryl, aralkyl, aryloxy, (C₁-C₁₀)alkylhydroxy,hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyl, (C₁-C₁₀)alkylamino, amino(C₁-C₁₀)alkyl, arylcarbonyl, (C₁-C₁₀)alkoxycarbonyl or aryloxycarbonyl;R⁷ represents hydrogen, (C₁-C₁₀)alkyl or (C₁-C₁₀)alkoxy;

[0043] R² and R³, which may be same or different, are each independentlyhydrogen, halo, (C₁-C₁₀)alkyl, halogenated(C₁-C₁₀)alkyl, hydroxyl or(C₁-C₁₀)alkoxy; and

[0044] R⁴ represents hydrogen atom, or substituted or unsubstitutedgroups selected from (C₁-C₁₀)acyl, thio(C₁-C₁₀)acyl,—C(═O)—(C₁-C₁₀)alkoxy, —C(═S)-cyclo(C₃-C₈)alkoxy,—C(═O)—(C₂-C₁₀)alkenyloxy, —C(═O)—(C₂-C₁₀)alkenyl, —C(═O)-aryloxy,—C(═S)—(C₁-C₁₀)alkoxy, —C(═S)—(C₂-C₁₀)alkenyloxy, —C(═S)-aryloxy,—C(═O)—C(═O)—(C₁-C₁₀)alkyl, —C(═O)—C(═O)-aryl,—C(═O)—C(═O)—(C₁-C₁₀)alkoxy, —C(═O)—C(═O)-aryloxy,—(C═S)—S—(C₁-C₁₀)alkyl, —(C═S)—NH₂, —(C═S)—NH—(C₁-C₁₀)alkyl,—C(═S)—N—((C₁-C₁₀)alkyl)₂, —C(═S)—NH—(C₂-C₁₀)alkenyl,(C═S)—(C═O)—(C₁-C₁₀)alkoxy, —(C═S)—(C═O)-aryloxy,—C(═S)—O—(C═O)—(C₁-C₁₀)alkyl, C(═S)—C(═S)—(C₁-C₁₀)alkyl,—C(═S)—C(═S)-aryl, thiomorpholinyl-C(═S)— or pyrrolidinyl-C(═S)—. In oneembodiment R² and R³ are each independently hydrogen, fluoro ortrifluoromethyl. Oxazolidinone derivatives of another group of thisembodiment have the above structure, wherein R^(N) is

[0045] In another embodiment R^(n) is

[0046] and R⁷ is hydrogen, (C₁-C₁₀)alkyl or (C₁-C₁₀)alkoxy.

[0047] Oxazolidinone derivatives of one group of this embodiment havethe above structure (Ia), wherein R^(N) is

[0048] in which R^(b) is hydrogen, substituted or unstubstituted(C₁-C₁₀)alkyl, halogenated (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl,(C₁-C₁₀)alkylhydroxy, hydroxy(C₁-C₁₀)alkyl, halogenated(C₁-C₁₀)alkylhydroxy, halogenated hydroxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylamino or amino (C₁-C₁₀)alkyl, the group of the structure

[0049] the group of the structure

[0050] the group of the structure

[0051] the group of the structure

[0052] the group of the structure

[0053] in which R′ is hydrogen, (C₁-C₁₀)alkyl or carboxy (C₁-C₁₀)alkyl;R⁶ is hydrogen, halogen or (C₁-C₁₀)alkoxy and m is ranging from 1 to 4.Specific non-limiting examples of the group R^(b) are

[0054] or R^(b) has the structure

[0055] in which R⁶ is hydrogen, fluoro or methoxy group,

[0056] or R^(b) has the structure

[0057] where R⁶ is hydrogen, fluoro or methoxy group.

[0058] Oxazolidinone derivatives of another group of this embodimenthave the above structure,

[0059] wherein R^(N) is

[0060] In another embodiment R^(N) is

[0061] and R^(b) is hydrogen or methyl.

[0062] Oxazolidinone derivatives of another group of this embodimenthave the above structure,

[0063] wherein R^(N) is

[0064] In another embodiment R^(N) is

[0065] and R^(b) is hydrogen, methyl, benzyl, p-methoxybenzyl, n-butyl,propenyl or methylhydroxy or Rb has the structure

[0066] Oxazolidinone derivatives of another group of this embodimenthave the above structure,

[0067] wherein R^(N) is

[0068] In another embodiment R^(N) is

[0069] and Rb is methyl. Oxazolidinone derivatives of another group ofthis embodiment have the above structure, wherein R^(N) is

[0070] In another embodiment R^(N) is

[0071] and Rb is methyl, benzyl, p-fluorobenzyl, p-fluorophenyl orphenyl.

[0072] Oxazolidinone derivatives of another group of this embodimenthave the above structure,

[0073] wherein R^(N) is

[0074] and R⁷ is hydrogen, (C₁-C₁₀)alkyl or (C₁-C₁₀)alkoxy.

[0075] The moiety R^(N) also has the structure

[0076] Oxazolidinone derivatives of another group of this embodimenthave the above structure, wherein R^(N) is

[0077] in which R^(b) is hydrogen, substituted or unsubstituted(C₁-C₁₀)alkyl, halogenated (C C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, aralkyl,(C₁-C₁₀)alkylcarbonyl, (C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl, (CC₁-C₁₀)alkylhydroxy, hydroxy(C₁-C₁₀)alkyl, dihydroxy(C₁-C₁₀)alkylhalogenated (C₁-C₁₀)alkylhydroxy, halogenated hydroxy(C₁-C₁₀)alkyl;wherein R⁴ is —C(═O)—H, substituted or unsubstituted—C(═O)—(C₁-C₁₀)alkyl, —C(═O)—(C₁-C₁₀)alkylhydroxy,—C(═O)-halogenated(C₁-C₁₀)alkyl, —C(═O)—(C₂-C₁₀)alkenyl, —C(═S)—H,—C(═S)—(C₁-C₁₀)alkyl, —C(═S)—(C₁-C₁₀)alkoxy, —C(═S)—NH₂, —C(═S)—(CC₁-C₁₀)alkylhydroxy, —C(═S)-halogenated(C₁-C₁₀)alkyl, —C(═S)-phenyl; andR² and R³ are each independently hydrogen, fluoro or trifluoromethylgroup.

[0078] Oxazolidinone derivatives of yet another group of this embodimenthave the above structure, wherein R^(N) is

[0079] in which R^(b) is hydrogen, methyl, ethyl, propyl, n-butyl,benzyl, p-methoxybenzyl, hydroxy ethyl (ethylhydroxy), methoxyethyl,propenyl,

[0080] and R⁴ is —C(═O)—H, —C(═O)—CH₃—C(═S)—CH₃, —C(═S)—OCH₃,—C(═S)—OCH₂CH₃. —C(═S)-(iso-propoxy) or —C(═S)—NH(pyridyl).

[0081] Oxazolidinone derivatives of yet another group of this embodimenthave the above structure, wherein R^(N) is

[0082] R⁴ is —C(═O)—H, substituted or unsubstituted—C(═O)—(C₁-C₁₀)alkyl, —C(═O)-halogenated(C₁-C₁₀)alkyl,—C(═O)—(C₂-C₁₀)alkenyl, —C(═O)—C(═O)—(C₁-C₁₀)alkoxy,—C(═O)—(C₁-C₁₀)alkoxy, —C(═S)—(C₁-C₁₀)alkyl, —C(═S)-halogenated(C₁-C₁₀)alkyl, —C(═S)—S—(C₁-C₁₀)alkyl, —C(═S)—(C₁-C₁₀)alkoxy,—C(═S)—O—C(═O)—(C₁-C₁₀)alkyl, —C(═S)—(C₃-C₈)cycloalkoxy,—C(═S)—(C₂-C₁₀)alkenyloxy, —C(═S)-pyrrolidinyl, —C(═S)—NH₂,—C(═S)—N((C₁-C₁₀)alkyl)₂, —C(═S)—NH—(C₂-C₁₀)alkenyl,—C(═S)-thiomorpholinyl; and R² and R³ are each independently hydrogen,fluoro or trifluoromethyl group.

[0083] Oxazolidinone derivatives of another embodiment have the abovestructure, where R^(n) has the structure

[0084] and

[0085] R² and R³ are each independently hydrogen, fluoro ortrifluoromethyl group and R⁴ is —C(═S)—CH₃, —C(═S)—CH₂—CH₃,—C(═S)—CH₂—CF₃, —C(═S)—S—CH₃, —C(═S)—O—CH₃, —C(═S)—O—CH₂—CH₃,—C(═S)—O—CH₂—CH₂—CH₃, —C(═S)—O-(iso-propyl), —C(═S)—O—CH₂—CF₃,—C(═S)—O-cyclohexyl, —C(═S)—O—CH₂—CH═CH₂, —C(═S)—CH₂—CH₂—N(CH₃)₂,—C(═S)—O—CH₂—CH₂OH, —C(═S)—CH₂—CH₂—OCH₃, —C(═S)—O—CS(═O)—CF₃,—C(═S)—NH², —C(═S)—NH—CH₂, C(═S)—NH—CH₂—CH₂—OH, —C(═S)—N(CH₂CH₃)₂,—C(═S)—NH—CH₂—CH═CH₂, —C(═S)—NH-benzyl, —C(═S)—NH-pyridyl,—C(═S)—NH-(p-methoxybenzyl), —C(═S)—NH—CH₂-pyridyl,—C(═S)-thiomorpholinyl,

[0086] Pharmaceutically acceptable salts forming part of this inventioninclude salts derived from inorganic bases such as Li, Na, K, Ca, Mg,Fe, Cu, Zn, Mn; salts of organic bases such asN,N′-diacetylethylenediamine, betaine, caffeine, 2-diethylaminoethanol,2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine,glucosamine, hydrabamine, isopropylamine, methylglucamine, morpholine,piperazine, piperidine, procaine, purines, theobromine, triethylamine,trimethylamine, tripropylamine, tromethamine, diethanolamine, meglumine,ethylenediamine, N,N′-diphenylethylenediamine,N,N′-dibenzylethylenediamine, N-benzyl phenylethylamine, choline,choline hydroxide, dicyclohexylamine, metformin, benzylamine,phenylethylamine, dialkylamine, trialkylamine, thiamine,aminopyrimidine, aminopyridine, purine, spermidine, and the like; chiralbases like alkylphenylamine, glycinol, phenyl glycinol and the like,salts of natural amino acids such as glycine, alanine, valine, leucine,isoleucine, norleucine, tyrosine, cystine, cysteine, methionine,proline, hydroxy proline, histidine, omithine, lysine, arginine, serine,threonine, phenylalanine; unnatural amino acids such as D-isomers orsubstituted amino acids; guanidine, substituted guanidine wherein thesubstituents are selected from nitro, amino, alkyl such as methyl,ethyl, propyl and the like; alkenyl such as ethenyl, propenyl, butenyland the like; alkynyl such as ethynyl, propynyl and the like; ammoniumor substituted ammonium salts and aluminum salts. Salts may include acidaddition salts where appropriate which are, sulphates, nitrates,phosphates, perchlorates, borates, halides, acetates, tartrates,maleates, citrates, succinates, palmoates, methanesulphonates,benzoates, salicylates, hydroxynaphthoates, benzenesulfonates,ascorbates, glycerophosphates, ketoglutarates and the like.Pharmaceutically acceptable solvates may be hydrates or comprising othersolvents of crystallization such as alcohols.

[0087] The compounds which are provided by way of illustration only andtherefore should not be construed to limit the scope of the inventionare:

[0088] or its steroisomers like (R) or mixture of (R) and (S) isomers;or pharmaceutically acceptable salts thereof.

[0089] Me represent methyl

[0090] Et represent ethyl

[0091] Pro represents propyl.

[0092] In the structures described herein whenever an open ended bond ispresent that represents a methyl group.

[0093] THP represent tetrahydropyranyl

[0094] The present invention also relates to a process for thepreparation of the compound of formula (I) where R¹ represents —NHR⁴,wherein R⁴ represents hydrogen atom and all other symbols are as definedearlier, which comprises:

[0095] (i) reacting a compound of formula (III)

[0096] where all the symbols are as defined earlier, with a compound offormula (IV)

[0097] where L represents a leaving group such as halogen atom,(C₁-C₁₀)alkoxy, such as methoxy, ethoxy, propoxy and the like; sulfonylgroups such as methylsulfonyl, ethylsulfonyl, p-toluenesulfonyl and thelike; R² and R³ are as defined earlier, to produce a compound of formula(V)

[0098] where Y¹, Y², Y³, R², R³ and Z are as defined earlier,

[0099] (ii) reducing the compound of formula (V) to produce a compoundof formula (VI)

[0100] where Y¹, Y², Y³, R², R³ and Z are as defined earlier,

[0101] (iii) reacting the compound of formula (VI) withalkylchloroformate, to produce a compound of formula (VII)

[0102] where R_(c) represents (C₁-C₁₀)alkyl group such as methyl, ethyl,propyl, and the like, or aralkyl group such as benzyl, allyl group andthe like; Y¹, Y², Y³, R², R³ and Z are as defined earlier,

[0103] (iv) reacting the compound of formula (VII) with a compound offormula (VIII)

[0104] where R¹² represents (C₁-C₁₀)alkyl group such as methyl, ethyl,propyl and the like, in the presence of a base to produce a compound offormula (I)

[0105] where R¹ represents hydroxy; Y₁, Y², Y³, R², R³ and Z are asdefined earlier,

[0106] (v) reacting the compound of formula (I) with(C₁-C₁₀)alkylsulfonyl chloride or aryl sulfonyl chloride to produce acompound of formula (I), where R¹ represents alkyl sulfonyl or arylsulfonyl, which in turn was reacted with NaN₃ to produce compound offormula (I)

[0107] where R represents azido; Y¹, Y², Y³, R², R³ and Z are as definedearlier and

[0108] (vi) reducing the compound of formula (I) wherein R¹ representsazido group, to produce compound of formula (I)

[0109] where R¹ represents —NHR⁴ wherein R⁴ represents hydrogen atom;Y¹, Y², Y³, R², R³ and Z are as defined earlier.

[0110] The reaction of a compound of formula (III) with a compound offormula (IV) to produce a compound of formula (V) may be carried outusing a base such as potassium hydroxide (KOH), sodium hydroxide (NaOH),potassium carbonate (K₂CO₃), sodium carbonate (Na₂CO₃), sodium hydride(NaH), potassium hydride (KH), triethylamine, diisopropylethyl amine andthe like. The reaction may be carried out using a solvent such asdimethylsulfoxide (DMSO), dimethylformamide (DMF), tetrahydrofuran(THF), acetonitrile, chloroform and the like or mixtures thereof. Thereaction may be carried out in inert atmosphere, which may be maintainedusing inert gases such as nitrogen (N²) or argon (Ar). The reaction maybe carried out at a temperature in the range of 20 to 100° C.,preferably at a temperature in the range of ambient to 80° C. Thereaction time may range from 1 to 15 h, preferably from 6 to 12 h.

[0111] The reduction of a compound of formula (V) to produce a compoundof formula (VI) may be carried out in the presence of gaseous hydrogenand a catalyst such as Ru, Pd, Rh, Pt, Ni on solid beads such ascharcoal, alumina, asbestos and the like. The reduction may be conductedin the presence of a solvent such as dioxane, acetic acid, ethylacetate, THF, alcohol such as methanol, ethanol and the like or mixturesthereof. A pressure between atmospheric pressure to 60 psi may be used.The reaction may be carried out at a temperature in the range of 25 to60° C., preferably at room temperature. The reaction time ranges from 2to 48 h. The reduction may also be carried out by employing metal inmineral acids such as Sn/HCl, Fe/HCl, Zn/HCl, Zn/CH₃CO₂H and the like.

[0112] The conversion of compound of formula (VI) to compound of formula(VII) may be carried out with alkylchloroformates such asmethychloroformate, ethylchloroformate, propylchloroformate,benzylchloroformate and the like. The solvent of the reaction may beselected from water, acetone, THF, acetonitrile, dichloromethane (DCM)and the like or mixtures thereof. The reaction may be carried out in thepresence of base such as K₂CO₃, Na₂CO₃, NaH, KOH, triethylamine (Et₃N)and the like. The temperature of the reaction may be carried out in thepresence of 0 to 60° C., preferably at 0° C. to room temperature. Thetime of the reaction is maintained in the range of 1-12 h, preferably inthe range of 1-4 h.

[0113] The reaction of a compound of formula (VII) with a compound offormula (VIII) to produce a compound of formula (I), where R¹ representshydroxy group, defined above may be carried out in the presence of abase such as alkali metal hydrides like NaH or KH or organolithiums likemethyllithium (CH₃Li), butyllithium (BuLi), lithium diisopropylamide(LDA) and the like or alkoxides such as sodiummethoxide (NaOMe),sodiumethoxide (NaOEt), potassium tert-butoxide (t-BuOK). The reactionmay be carried out in the presence of a solvent such as THF, dioxane,DMF, DMSO, ethylene glycol dimethylether (DME) and the like or mixturesthereof. Hexamethylphosphamide (HMPA) may be used as a cosolvent. Thereaction temperature may range from −78 to 150° C., preferably at atemperature in the range of −78 to 30° C. The duration of the reactionmay range from 3 to 12 h.

[0114] The compound of formula (I) where R¹ represents OH is convertedto compound of formula (I) where R¹ represents alkylsulfonyl orarylsulfonyl by treating with alkylsulfonylchloride orarylsulfonylchloride such as methanesulfonyl chloride, p-toluenesulfonylchloride and the like. The reaction may be carried out in the presenceof chloroform, DCM, THF, dioxane and the like or mixtures thereof. Thebase used in the reaction may be selected from Et3N, diisopropylethylamine, Na₂CO₃, K₂CO₃ and the like. The temperature of the reactionis maintained in the range of 0 to 50° C., preferably in the range of 0to room temperature. The time of the reaction should be maintained inthe range of 1-12h, preferably in the range of 1-4h. The compound offormula (I) where R¹ represents alkylsulfonyl or arylsulfonyl isconverted to compound of formula (I) where R¹ represents azido group, bytreating with sodium azide (NaN₃) or lithium azide (LiN₃). The solventused in the reaction may be selected from DMF, DMSO, acetonitrile andthe like. The temperature of the reaction is maintained in the range ofroom temperature to 120° C., preferably room temperature to 80° C. Thetime of the reaction is maintained in the range of 1-12 h, preferably1-4 h.

[0115] The reduction of a compound of formula (I) where R¹ representsazido group, to produce a compound of formula (I) where R¹ represents—NHR⁴ wherein R⁴ represents hydrogen atom, may be carried out in thepresence of gaseous hydrogen and a catalyst such as Ru, Pd, Rh, Pt, Nion solid beads such as charcoal, alumina, asbestos and the like. Thereduction may be conducted in the presence of a solvent such as dioxane,acetic acid, ethyl acetate, THF, alcohol such as methanol, ethanol andthe like or mixtures thereof. A pressure between atmospheric pressure to60 psi may be used. The reaction may be carried out at a temperature inthe range of 25 to 60° C., preferably at room temperature. The reactiontime ranges from 2 to 48 h. The reduction may also be carried out byemploying PPh₃ in water.

[0116] In still another embodiment of the present invention there isprovided another process for the preparation of compound of formula (I)where R¹ represents hydroxy and all the symbols are as defined earlier,which comprises:

[0117] (i) reacting the compound of formula (VI)

[0118] where all the symbols are as defined earlier, with a compound offormula (IX)

[0119] where R¹ represents hydroxy, to produce a compound of formula (X)

[0120] where R¹ represents hydroxy; Y¹, Y², Y³, R², R³ and Z are asdefined earlier, and

[0121] (ii) carbonylating the compound of formula (X) with a suitablecarbonylating agent to produce the compound of formula (I) where R¹represents hydroxy and all other symbols are as defined above.

[0122] The reaction of a compound of formula (VI) defined above with acompound of formula (IX) defined above to produce a compound of formula(X) may be carried out in the presence or absence of a base such asK₂CO₃, NaH, t-BuOK and the like or mixtures thereof. The reaction may becarried out in the presence of a solvent such as DMF, toluene, THF,acetonitrile and the like or mixtures thereof. The reaction may also becarried out in the presence of Lewis acids such as BF₃.OEt₂, ZnC₁₂,Ti(OiPr)₄, lanthanide metal complexes and the like in the presence ofdichloroethylene (DCE), DMF, THF and the like or mixtures thereof. Thereaction temperature may be in the range of 0 to 120° C., preferably ata temperature in the range of 0 to 100° C. The reaction time may rangefrom 3 to 24 h, preferably from 4 to 12 h.

[0123] The conversion of compound of formula (X) to a compound offormula (I) may be carried out using a carbonylating agent such asdialkyl carbonate, dihalo carbonyl, 1,1′-carbonyldiimidazole and thelike in the presence or absence of a base. The base may be selected fromtriethylamine, tributylamine, diisopropylethylamine,1,4-diazabicyclo[2.2.2]octane (DABCO),1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),1,1,5-diazabicyclo[4.3.0]non-5-ene (DBN), alkoxides like NaOMe, NaOEtand the like or the inorganic base such as NaOH, KOH and the like. Thereaction may be carried out in the presence of a solvent such asdichloromethane, THF, DMF, ethyl acetate and the like or mixturesthereof. The reaction temperature may be in the range of −20 to 135° C.,preferably at a temperature in the range of 15 to 80° C. The reactiontime may range from 2 to 72 h, preferably from 2 to 50 h.

[0124] In still another embodiment of the present invention there isprovided yet another process for the preparation of compound of theformula (I) where R¹ represents azido and all other symbols are asdefined earlier, which comprises:

[0125] (i) reacting a compound of formula (VII)

[0126] where R^(c) represents (C₁-C₁₀)alkyl group such as methyl, ethyl,propyl, and the like; or aralkyl group such as benzyl, allyl group andthe like; and all other symbols are as defined earlier, with a compoundof formula (XI)

[0127] where L represents a leaving group such as halogen atom,(C₁-C₁₀)alkoxy group such as methoxy, ethoxy, propoxy and the like, orsulphonyl group such as methylsulfonyl, ethylsulfonyl, p-toluenesulfonyland the like; to produce a compound of formula (XII)

[0128] where R^(c), Y¹, Y², Y³, R², R³ and Z are as defined earlier,

[0129] (ii) converting the compound of formula (XII) defined above to acompound of formula (XIII)

[0130] where Y¹, Y², Y³, R², R³ and Z are as defined earlier, and

[0131] (iii) converting the compound of formula (XIII) defined above toa compound of formula (I) by reacting with organic or inorganic azide,

[0132] where R¹ represents azido group; Y¹, Y², Y³, R², R³ and Z are asdefined earlier.

[0133] The reaction of a compound of formula (VII) with a compound offormula (XI) may be carried out in the presence of base such as NaH, KH,K₂CO₃, t-BuOK, LDA, NaOMe, with or without phase transfer catalyst suchas tetrabutylammonium halide and the like. The reaction may be carriedout in the presence of a suitable solvent such as THF, DMF, DMSO,benzene and the like or mixtures thereof. The reaction may be carriedout at a temperature in the range of −78 to 120° C., preferably at −78to 60° C. The reaction time may range from 2 to 20 h, preferably from 4to 10 h.

[0134] The conversion of a compound of formula (XII) to a compound offormula (XIII) defined above may be carried in the presence of reagentssuch as I₂, KI, or NaI. The reaction may be carried out in the presenceof a solvent such as chloroform (CHCl₃), dichloromethane (CH₂Cl₂), THF,DMF, DMSO, acetonitrile and the like or mixtures thereof. The reactiontemperature may be in the range of 0 to 100° C., preferably at ambienttemperature. The reaction time may range from 2 to 24 h, preferably from2 to 12 h.

[0135] The conversion of a compound of formula (XIII) to a compound offormula (I) where R¹ represents azido group, may be carried out in thepresence of one or more equivalents of metal azide such as LiN₃, NaN₃ ortrialkyl silylazide. The reaction may be carried out in the presence ofsolvent such as THF, acetone, DMF, DMSO and the like or mixturesthereof. The reaction may be carried out in inert atmosphere, which maybe maintained using N₂ or Ar. The reaction may be carried out at atemperature in the range of ambient temperature to reflux temperature ofthe solvent, preferably at a temperature in the range of 50 to 80° C.The reaction time may range from 0.5 to 18 h, preferably 1 to 4 h.

[0136] In yet another embodiment of the present invention, there isprovided a process for the preparation of compound of formula (I), whereR¹ represents hydroxy group and all other symbols are as definedearlier, which comprises:

[0137] (i) reacting a compound of formula (VII)

[0138] where all the symbols are as defined earlier, with a compound offormula (XIV)

[0139] where L represents a leaving group such as halogen atom,(C₁-C₁₀)alkoxy group such as methoxy, ethoxy, propoxy and the like,sulphonyl group such as methylsulfonyl, ethylsulfonyl, p-toluenesulfonyland the like; to produce a compound of formula (XV)

[0140] where R^(c), Y¹, Y², Y³, R², R³ and Z are as defined earlier,

[0141] (ii) hydrolysing the acetonide moiety in the compound of formula(XV) using conventional methods to produce a compound of formula (XVI)

[0142] where R^(c), Y¹, Y², Y³, R², R³ and Z are as defined earlier, and

[0143] (iii) cyclising the compound of formula (XVI) with or without abase to a compound of formula (I)

[0144] where R¹ represents hydroxy group and all other symbols are asdefined earlier.

[0145] The reaction of a compound of formula (VII) with a compound offormula (XIV) to produce a compound of formula (XV) may be carried outin the presence of a base. The base employed may be selected from K₂CO₃,NaH, t-BuOK, LDA and the like. The reaction may be carried out in thepresence of a solvent such as DMF, THF, DMSO, methanol, ethanol,propanol, iso-propanol and the like. The reaction may be carried at atemperature in the range of −78 to 120° C., preferably at a temperaturein the range of −78 to 100° C. The reaction time may range from 2 to 24h, preferably from 2 to 20 h.

[0146] The hydrolysis of a compound of formula (XV) to produce acompound of formula (XVI) may be carried out using dilute mineral acidsuch as hydrochloric acid (HCl), sulfuric acid (H₂SO₄) and the like,organic acids such as aqueous acetic acid, p-toluene sulfonic acid,camphorsulfonic acid, trifluoro acetic acid and the like. The reactionmay be carried out in the presence of suitable solvent such as water,methanol, THF, dioxane and the like or mixtures thereof. The reactionmay be carried at a temperature in the range of 30 to 100° C.,preferably at a temperature in the range of 30 to 60° C. The reactiontime may range from 10 min to 5 h, preferably from 30 min to 2.5 h.

[0147] The conversion of a compound of formula (XVI) to a compound offormula (I) where R¹ represents hydroxy group, may be carried out byusing a base such as NaOMe, K₂CO₃, NaH and the like, in presence of thea solvent such as methanol, ethanol, propanol, isopropanol, DMF, THF,and the like. The duration and temperature of the reaction aremaintained in the range of 2 to 4 h and room temperature to 150° C.respectively.

[0148] In still another embodiment of the present invention there isprovided yet another process for the preparation of compound of theformula (I) where R¹ represents hydroxy group and all other symbols areas defined earlier, which comprises:

[0149] (i) converting the compound of formula (XII)

[0150] where R^(c), Y², Y³, R², R³ and Z are as defined earlier, to acompound of formula (XVI)

[0151] where R^(c), Y¹, Y², Y³, R², R³ and Z are as defined earlier, and

[0152] (ii) cyclising the compound of formula (XVI) with or without abase to a compound of formula (I)

[0153] where R¹ represents hydroxy group and all other symbols are asdefined earlier.

[0154] The conversion of a compound of (XII) to a compound of formula(XVI) may be carried out by treating with OsO₄, KMnO₄ and the otherrelated reagents. The reaction may be carried out in the presence ofco-oxidant such as N-methylmorpholine N-oxide, t-butylhydroperoxide,barium chloride and the like.

[0155] The conversion of a compound of formula (XVI) to a compound offormula (I) where R¹ represents hydroxy group, may be carried out byusing a base such as NaOMe, K₂CO₃, NaH and the like, in presence of thea solvent such as methanol, ethanol, propanol, isopropanol, DMF, THF,and the like. The duration and temperature of the reaction aremaintained in the range of 2 to 4 h and room temperature to 150° C.respectively.

[0156] In still another embodiment of the present invention there isprovided a process for the preparation of compounds of formula (I) whereR¹ represents azido group and all other symbols are as defined earlier,which comprises:

[0157] (i) reacting a compound of formula (VII)

[0158] where all the symbols are as defined earlier, with a compound offormula (XVII)

[0159] where L represents a leaving group such as halogen atom,(C₁-C₁₀)alkoxy group such as methoxy, ethoxy, propoxy and the like, orsulphonyl group such as methylsulfonyl, ethylsulfonyl, p-toluenesulfonyland the like; to produce a compound of formula (XVIII)

[0160] where R^(c), Y¹, Y², Y₃, R², R³ and Z are as defined earlier, and

[0161] (ii) converting the compound of formula (XVIII) defined above toa compound of formula (I) by reacting with an organic or an inorganicazide,

[0162] where R¹ represents azido group; Y¹, Y², Y³, R², R³ and Z are asdefined earlier,

[0163] The reaction of a compound of formula (VII) defined above with acompound of formula (XVII) defined above may be carried out in thepresence of a base such as NaH, NaOMe, K₂CO₃, n-BuLi, LDA and the like.The reaction may be carried out in the presence of a solvent such asDMF, THF, DMSO, benzene and the like or mixtures thereof. The reactionmay be carried out at a temperature in the range of −78 to 70° C.preferably at a temperature in the range of −78 to 50° C. The reactiontime may range from 1 to 15 h preferably 1 to 10 h.

[0164] The conversion of a compound of formula (XVIII) to a compound offormula (I) where R¹ represents azido group, may be carried out in thepresence of one or more equivalent of metal azide such as LiN₃, NaN₃ ortrialkyl silylazide. The reaction may be carried out in the presence ofsolvent such as THF, acetone, DMF, DMSO and the like or mixturesthereof. The reaction may be carried out in inert atmosphere, which maybe maintained by using N₂ or Ar. The reaction may be carried out at atemperature in the range of ambient temperature to reflux temperature ofthe solvent, preferably at a temperature in the range of 50 to 80° C.The reaction time may range from 0.5 to 18 h, preferably 1 to 4 h.

[0165] In still another embodiment of the present invention there isprovided yet another process for the preparation of compound of theformula (I), where R¹ represents —NHR⁴, wherein R⁴ represents acetylgroup and all other symbols are as defined earlier, which comprises:

[0166] (i) reacting a compound of formula (VII)

[0167] where all the symbols are as defined earlier, with a compound offormula (XIX)

[0168] to produce a compound of formula (I)

[0169] where R¹ represents —NHR⁴, where R⁴ represents acetyl group; andY¹, Y², Y³, R², R³ and Z are as defined earlier.

[0170] The compound of formula (VII) defined above may be converted to acompound of formula (I) defined above, by reacting with compound offormula (XIX) in presence of a base such as NaH, LDA, BuLi and the like.The reaction may be carried out at a temperature in the range of −78 to1 00° C., preferably in the range of −78 to 80° C. The reaction time mayrange from 3 to 10 h.

[0171] Another embodiment of the present invention provides a processfor the preparation of compound of formula (I), which comprises:

[0172] (i) reacting the compound of formula (VI),

[0173] where all symbols are as defined earlier, to a compound offormula (VIa)

[0174] where X represents halogen atom such as fluorine, chlorine,bromine or iodine and all other symbols are as defined earlier,

[0175] (ii) reacting the compound of formula (VIa), with a compound offormula (IXa)

[0176] where R1 is as defined earlier, to obtain a compound of formula(I)

[0177] where all symbols are as defined earlier.

[0178] The compound of formula (VI) is converted to a compound offormula (VIa), by reacting with sodium nitrite, in the presence of acidand cuprous halide such as cuprous bromide and the like. The temperatureof the reaction is maintained in the range of 0 to 60° C., preferably10° C. The duration of the reaction is maintained in the range of 1 to12 h, preferably 1-2 h.

[0179] The compound of formula (VIa) is reacted with a compound offormula (IXa), to obtain a compound of formula (I), in the presence ofsolvent such as dioxane, DMF, THF and the like. The reaction may becarried out in the presence of amine ligand such ascyclohexane-1,2-diamine, ethylene diamine and the like. The temperatureof the reaction is maintained in the range of 60 to 140° C., preferablyreflux temperature of the solvent used. The duration of the reaction ismaintained in the range of 2 to 24 h, preferably 12 h.

[0180] In yet another embodiment of the present invention there isprovided a process for the preparation of compound of formula (I), whereR¹ represents —NHR⁴, wherein R⁴ represents formyl group; from compoundof formula (I) where R¹ represents —NHR⁴ wherein R⁴ represents hydrogenatom,

[0181] where all other symbols are as defined earlier.

[0182] The reaction of compound of formula (I) where R¹ represents —NHR⁴wherein R⁴ represents hydrogen atom, to produce a compound of formula(I), where R¹ represents —NHR⁴, wherein R⁴ represents formyl group, maybe carried out in presence of alkyl formates such as methyl formate,ethyl formate and the like. The duration of the reaction may range from4 to 48 h, prefereably 12 to 24 h. The reaction may be carried out at atemperature in the range of 60 to 1 20° C., preferably at refluxtemperature.

[0183] In another embodiment of the present invention there is provideda process for the preparation of compound of formula (I), where R¹represents —NHR⁴, wherein R⁴ represents —C(═O)—R^(4a), where R^(4a)represents (C₁-C₁₀)alkyl, (C₁-C₁₀)lkoxy, (C₂-C₁₀)alkenyl,halo(C₁-C₁₀)alkyl, aryloxy, (C₂-C₁₀)alkenyloxy, aryloxy-C(═O)— or(C₁-C₁₀)alkoxy-C(═O)—; from a compound of formula (I) where R¹represents —NHR⁴ wherein R⁴ represents hydrogen atom,

[0184] where all other symbols are as defined earlier.

[0185] The above conversion may be carried out by treating the startingmaterial with appropriate halide such as acetyl chloride like acetylchloride, propionyl chloride and the like; (C₁-C₁₀)alkylchloroformatelike methylchloroformate, ethylchloroformate and the like;aralkylchloroformate like benzylchloroformate and the like. The reactionmay be carried out in the presence of a solvent such as CH₂Cl₂, CHCl₃,toluene, THF and the like or mixtures thereof. The reaction may becarried out in the presence of a base like Et₃N, diisopropyl ethylamine,K₂CO₃, NaH, KOt-Bu and the like. The reaction may be carried at atemperature in the range of −20 to 60° C., preferably at a temperaturein the range of 0 to room temperature. The reaction time may range from1 to 12 h, preferably from 1 to 4 h.

[0186] Alternatively, the compound of formula (I), where R¹ represents—NHR⁴ wherein R⁴ represents acetyl group, may be prepared by reactingcompound of formula (I) where R¹ represents azido group, by treatingwith thioacetic acid.

[0187] The compound of formula (I) where R¹ represents azido group maybe converted to a compound of formula (I) where R¹ represents NHR⁴wherein R⁴ represents acetyl group by using thioacetic acid, with orwithout using a solvent such as THF, DMF, toluene and the like. Thereaction may be carried out at a temperature in the range of 25 to 40°C., preferably at room temperature. The reaction may range from 3 to 24h, preferably from 4 to 12 h.

[0188] In another embodiment of the present invention there is provideda process for the preparation of compound of formula (I), where R¹represents NHR⁴, wherein R⁴ represents —C(═S)—R^(4b), wherein R^(4b)represents (C₁-C₁₀)alkyl, halo(C₁-C₁₀)alkyl, —C(═O)—(C₁-C₁₀)alkoxy,—C(═O)-aryloxy, —C(═S)—(C₁-C₁₀)alkyl or —C(═S)-aryl; from compound offormula (I), where R¹ represents NHR⁴, wherein R⁴ represents—C(═O)—R^(4b), wherein R^(4b) represents (C₁-C₁₀)alkyl,halo(C₁-C₁₀)alkyl, C(═O)—(C₁-C₁₀)alkoxy, —C(═O)-aryloxy,—C(═S)—(C₁-C₁₀)alkyl or —C(═S)-aryl.

[0189] where all symbols are as defined earlier.

[0190] The above conversion may be carried out by taking a solution ofthe amide and Lawesson's reagent(2,4-bis(methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide) indry dioxane, toluene, THF, DMF and the like. The reaction may be carriedat a temperature in the range of room temperature to 130° C., preferablyat a temperature in the range of 55 to 90° C. The reaction time mayrange from 3 to 24 h, preferably from 3 to 10 h.

[0191] In another embodiment of the present invention there is provideda process for the preparation of compound of formula (I), where R¹represents —NHR⁴, wherein R⁴ represents —C(═S)—SR^(4c), wherein R^(4c)represents (C₁-C₁₀)alkyl group; from compound of formula (I) where R¹represents —NHR⁴ wherein R⁴ represents hydrogen atom,

[0192] where all other symbols are as defined earlier.

[0193] The compound of fomula (I), where R¹ represents —NHR⁴, wherein R⁴represents —C(═S)—SR^(4c), wherein R^(4c) represents (C₁-C₁₀)alkylgroup, may be prepared from compound of formula (I) where R¹ represents—NHR⁴ wherein R⁴ represents hydrogen atom, by using CS₂ in the presenceof a base such as Et₃N, diisopropyl ethylamine, K₂CO₃, NaH, t-BuOK andthe like, followed by the appropriate alkylhalide such as methyliodide,ethylbromide, propylbromide and the like. The reaction may be carriedout in the presence of a solvent such as water, ethanol, methanol,isopropanol, acetonitrile and the like, or mixtures thereof. Thereaction may be carried at a temperature in the range of roomtemperature to 60° C., preferably at room temperature. The reaction timemay range from 6 to 24h.

[0194] In another embodiment of the present invention there is provideda process for the preparation of compound of formula (I), where R¹represents —NHR⁴, wherein R⁴ represents —C(═S)—OR^(4d), R^(4d)represents (C₁-C₁₀)alkyl, (C₃-C₈)cycloalkyl, —(C═O)—(C₁-C₁₀)alkyl groupsubstituted with fluorine; aryl such as phenyl or napthyl and the like;halo(C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl or(C₂-C₁₀)alkenyl, which comprises:

[0195] (i) converting the compound of formula (I) where R¹ represents—NHR⁴ wherein R⁴ represents hydrogen atom, to a compound of formula (I)where R¹ represents isothiocyanate group,

[0196] where all other symbols are as defined earlier,

[0197] (ii) converting the compound of formula (I) where R¹ representsisothiocyanate group, to a compound of formula (I) where R¹ represents—NHR⁴, wherein R⁴ represents —C(═S)—OR^(4d), wherein R^(4d) represents(C₁-C₁₀)alkyl, (C₃-C₈)cycloalkyl, —(C═O)—(C1-C10)alkyl group substitutedwith fluorine; aryl, halo(C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkoxy(C1-C10)alkyl or (C₂-C₁₀)alkenyl group and all othersymbols are as defined earlier.

[0198] The compound of fomula (I) where R¹ represents isothiocyanategroup, may be prepared from compound of formula (I) where R¹ represents—NHR⁴ wherein R⁴ represents hydrogen atom, by using thiophosgene, in thepresence of a base such as Et₃N, K₂CO₃, NaOH and the like. The reactionmay be carried out in the presence of a solvent such as ethanol,methanol, isopropanol, CH₂Cl₂, acetonitrile and the like. The reactionmay be carried at a temperature in the range of 0 to 60° C., preferablyat 0C. The reaction may be carried out in an inert atmosphere usingargon or any other inert gas. The reaction time may range from 3 to 24h.

[0199] The compound of formula (I) where R¹ represents —NHR⁴, wherein R⁴represents —C(═S)—OR^(4d), wherein R^(4d) represents (C₁-C₁₀)alkyl,(C₃-C₈)cycloalkyl, —(C═O)—(C₁-C₁₀)alkyl group substituted with fluorine;aryl, halo(C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl or (C₂-C₁₀)alkenyl, is prepared from thecompound of formula (I) where R¹ represents isothiocyanate group, byusing respective alcohol such as methanol, ethanol, propanol,cylcohexanol and the like, in the presence of a base such as NaH, KH andthe like. The reaction may be carried out in the presence of a solventsuch as THF, toluene, DMF and the like. The reaction may be carried at atemperature in the range of room temperature to 130° C., preferably atreflux temperature of the solvent used. The reaction time may range from6 to 24 h.

[0200] In another embodiment of the present invention there is provideda process for the preparation of compound of formula (I), where R¹represents —NHR⁴, wherein R⁴ represents —C(═S)—N(R′R″), wherein R′represents hydrogen, (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, substituted orunsubstituted aralkyl, heteroaralkyl, hydroxy(C₁-C₁₀)alkyl, R′represents hydrogen or (C₁-C₁₀)alkyl or the two R′ and R″ groupstogether form a 5 or 6 membered cyclic structures containing one or twohetero atoms; from a compound of formula (I) where R¹ representsisothiocyanate group,

[0201] where all other symbols are as defined earlier.

[0202] The compound of formula (I), where R¹ represents —NHR⁴, whereinR⁴ represents —C(═S)—N(R′R″), where in R′ and R″ independently representhydrogen, is prepared by passing ammonia gas into a solution of compoundof formula (I) where R¹ represents isothiocyanate group, by using asolvent such as THF, toluene, and the like. The reaction may be carriedat a temperature in the range of —10° C. to room temperature, preferablyat −10° C. The reaction time may range from 20 min to 4 h, preferably 30min. The compound of formula (I), where R¹ represents —NHR⁴, wherein R⁴represents —C(═S)—N(R′R″), R′ represents hydrogen, (C₁-C₁₀)alkyl,alkenyl, substituted or unsubstituted aralkyl, heteroaralkyl,hydroxy(C₁-C₁₀)alkyl, R″ represents hydrogen or alkyl or R′ and R″groups together form a 5 or 6 membered cyclic structures containing oneor two hetero atoms, is prepared by treating compound of formula (I)where R¹ represents isothiocyanate group, by using appropriate aminesuch as methylamine, ethylamine, dimethylamine, diethylamine,benzylamine, aniline, proline, morpholine, thiomorpholine,pyridiylmethylamine and the like, in the presence of a solvent such asTHF, DMF, toluene, and the like. The reaction may be carried at atemperature in the range of room temperature to 140° C., preferably at60 to 100° C. The reaction time may range from 1 to 24 h, preferably 4to 12 h.

[0203] In yet another embodiment of the present invention there isprovided a process for the preparation of compound of formula (I) whereZ represents NR^(b) wherein R^(b) represents hydrogen, Y¹ represents‘═O’ group, Y² and Y³ independently represent hydrogen atom, from acompound of formula (I) where Z represents NR^(b) wherein R^(b)represents (C₁-C₁₀)alkyl group substituted with hydroxy group, Y¹represents ‘═O group’, Y² and Y³ independently represent hydrogen atom,

[0204] where all other symbols are as defined earlier.

[0205] The compound of formula (I) where Z represents NR^(b) whereinR^(b) represents hydrogen, Y¹ represents ‘═O’ group, Y² and Y³independently represent hydrogen atom, from a compound of formula (I)wherein Z represents NR^(b) wherein R^(b) represents (C₁-C₁₀)alkyl groupsubstituted with hydroxy group at the α-position, Y¹ represents ‘═Ogroup’, Y² and Y³ independently represent hydrogen atom, may be preparedby treating with a base such as triethylamine, di-isopropylamine,di-isopropylethylamine, pyridine, piperidine, 4-dimethylaminopyridine(DMAP), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), LDA, potassiumbis-(trimethyl silyl)amide, BuLi, Na₂CO₃, K₂CO₃, NaOH, KOH, NaOMe,NaOEt, NaOiPr, t-BuOK, NaH, KH and the like. The solvents used in thereaction may be selected from THF, ether, dioxane, toluene, benzene,DMF, DMSO, acetonitrile and the like. The temperature of the reactionmay be maintained in the range of −20 to 150° C., preferably in therange of −10 to 100° C. The duration of the reaction may be in the rangeof 0.2 to 64 h, preferably in the range of 1 to 48 h.

[0206] In still another embodiment of the present invention there isprovided a process for the preparation of compound of formula (I), whereZ represents NR^(b) wherein R^(b) represents substituted orunsubstituted (C₁-C₁₀)alkyl or aralkyl, Y¹ represents ‘═O group’, Y² andY³ independently represent hydrogen atom; from a compound of formula (I)where Z represents NR^(b) wherein R^(b) represents hydrogen, Y¹represents ‘═O’ group, Y² and Y³ independently represent hydrogen atom,

[0207] where all other symbols are as defined earlier.

[0208] The compound of formula (I), wherein Z represents NR^(b) whereinR^(b) represents substituted or unsubstituted (C₁-C₁₀)alkyl or aralkyl,Y¹ represents ‘═O group’, Y² and Y³ independently represent hydrogenatom, from a compound of formula (I) wherein Z represents NR^(b) whereinR^(b) represents hydrogen, Y¹ represents ‘═O’ group, Y² and Y³independently represent hydrogen atom, may be carried out in thepresence of a base such as triethylamine, di-isopropylamine,di-isopropylethylamine, pyridine, piperidine, DMAP,1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), LDA, potassium bis-(trimethylsilyl)amide, BuLi, Na₂CO₃, K₂CO₃, NaOH, KOH, NaOMe, NaOEt, NaOiPr,t-BuOK, NaH, KH and the like, followed by reacting with alkyl halidesuch as methyliodide, methoxymethylchloride, allylbromide, benzylbromideand the like. The solvent used in the reaction may be selected from DMF,DMSO, THF, dioxane, benzene, toluene and the like. The temperature ofthe reaction may be maintained in the range of −5 to 150° C., preferablyin the range of 0° C. to reflux temperature of the solvent. The duraionof the reaction may be in the range of 0.2 to 48 h, preferably in therange of 0.5 to 24 h.

[0209] In another embodiment of the present invention there is provideda process for the preparation of a compound of formula (I) where R¹represents halogen, from compound of formula (I) where R¹ representshydroxy group,

[0210] where all other symbols are as defined above.

[0211] The compound of formula (I) where R¹ represents halogen isprepared from compound of formula (I) where R¹ represents hydroxy groupmay be carried out by treating with tetrahalomethane group such as CBr₄,CCl₄ and the like, in the presence of PPh₃, P(alkyl)₃ and the like. Thereaction may be carried out in the presence of a solvent such as drydichloromethane, chloroform, tetrachloromethane, benzene, DMF, DMSO, THFand the like. The temperature of the reaction may be maintained in therange of 0 to 60° C., preferably at room temperature. The duration ofthe reaction may be in the range of 2 to 24 h, preferably 8 to 13 h.

[0212] In another embodiment of the present invention there is provideda process for the preparation of a compound of formula (I) where R¹represents ‘SH’, from compound of formula (I) where R¹ representshalogen atom,

[0213] where all other symbols are as defined above, which comprises

[0214] (i) reacting the compound of formula (I) where R¹ representshalogen atom, to produce a compound of formula (XX),

[0215] where all other symbols are as defined earlier, with a base andthioacetic acid,

[0216] (ii) reacting the compound of formula (XX), to produce a compoundof formula (I) where R¹ represents ‘SH’ group and all other symbols areas defined earlier, with base.

[0217] The compound of formula (XX) is prepared from compound of formula(I) where R¹ represents hydroxy group is prepared by using thioaceticacid in the presence of a base such as triethylamine, di-isopropylamine,di-isopropylethylamine, pyridine, piperidine, DMAP, DBU, LDA, potassiumbis-(trimethyl silyl)amide, BuLi, Na₂CO₃, K₂CO₃, NaOH, KOH, NaOMe,NaOEt, NaOiPr, t-BuOK, NaH, KH and the like. The solvent used in thereaction may be seleceted from THF, benzene, dioxane and the like. Thetemperature of the reaction is maintained in the range of roomtemperature to reflux temperature, preferably at reflux temperature. Theduration of the reaction is maintained in the range of 2 to 24 h,preferably 6 h.

[0218] The compound of formula (I), where R¹ represents ‘SH’ group isprepared from compound of formula (XX) by reacting with a base such asK₂CO₃, NaOH, KOH, BuLi and the like. The reaction may be carried out ata temperature in the range of room temperature to reflux temprature. Theduration of the reaction may be in the range of 1 to 24h.

[0219] In still another embodiment of the present invention there isprovided a novel intermediate of the formula (VII)

[0220] where R^(c) represents (C₁-C₁₀)alkyl group such as methyl, ethyl,propyl, and the like; aralkyl group such as benzyl, allyl group and thelike; R² and R³, which may be the same or different, are eachindependently hydrogen, halogen, (C₁-C₁₀)alkyl, halogenated(C₁-C₁₀)alkyl, cyano, nitro, SR^(a), NR^(a), or OR^(a), in which R^(a)is hydrogen, (C₁-C₁₀)alkyl or halogenated (C₁-C₁₀)alkyl;

[0221] is a heterocyclic moiety in which

[0222] is a 5-membered heterocyclic skeleton, Z represents O, S, ═CH,—CH₂ or NR^(b), R^(b) is hydrogen or a moiety, which may be substitutedor unsubstituted, straight chain or branched, selected from the groupconsisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, (C₃-C₈)cycloalkyl,hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy, (C₁-C₁₀)alkylamino,amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl, aryloxy, (C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀)alkoxycarbonyl and aryloxycarbonyl;

[0223] Y¹ represents ═O or ═S group and Y² and Y³ independentlyrepresent hydrogen, halogen, cyano, nitro, formyl, hydroxy, amino, ═O,═S group or substituted or unsubstituted groups selected from(C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyl,(C₁-C₁₀)alkoxycarbonyl, arylcarbonyl, carboxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylsulfonyl, (C₁-C₁₀) alkylcarbony(C₁-C₁₀)alkyl,arylcarbonylamino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyloxy(C₁-C₁₀)alkyl,amino(C₁-C₁₀)alkyl, mono(C₁-C₁₀)alkylamino, di(C₁-C₁₀)alkylamino,arylamino, (C₁-C₁₀)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl or heterocycloalkyl; Y² and Y³ when presenton adjacent carbon atoms together may also form a substituted orunsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure,optionally containing one or two hetero atoms selected from oxygen,sulfur or nitrogen.

[0224] The novel intermediate of formula (VII) may be prepared by aprocess, which comprises:

[0225] (i) reacting a compound of formula (III)

[0226] where all the symbols are as defined earlier, with a compound offormula (IV)

[0227] where L represents a leaving group such as halogen atom,(C₁-C₁₀)alkoxy group such as methoxy, ethoxy, propoxy and the like, orsulphonyl group such as methylsulfonyl, ethylsulfonyl, p-toluenesulfonyland the like; and the like; R² and R³ are as defined earlier, to producea compound of formula (V)

[0228] where Y¹, Y², Y³, R², R³ and Z are as defined earlier,

[0229] (ii) reducing the compound of formula (V) to produce a compoundof formula (VI)

[0230] where Y¹, Y², Y³, R², R³ and Z are as defined earlier,

[0231] (iii) reacting the compound of formula (VI) withalkylchloroformate, to produce a compound of formula (VII)

[0232] where R^(c), Y¹, Y², Y³, R², R³ and Z are as defined above,

[0233] The reaction of a compound of formula (III) with a compound offormula (IV) to produce a compound of formula (V) may be carried outusing a base such as KOH, NaOH, K₂CO₃, Na₂CO₃, NaH, KH, triethylamine,diisopropylethyl amine and the like. The reaction may be carried outusing a solvent such as DMSO, DMF, THF, acetonitrile, chloroform and thelike or mixtures thereof. The reaction may be carried out in inertatmosphere, which may be maintained using inert gases such as N₂ or Ar.The reaction may be carried out at a temperature in the range of 20°C.-100° C., preferably at a temperature in the range of ambient to 80°C. The reaction time may range from 1 to 15 h, preferably from 6 to 12h.

[0234] The reduction of a compound of formula (V) to produce a compoundof formula (VI) may be carried out in the presence of gaseous hydrogenand a catalyst such as Ru, Pd, Rh, Pt, Ni on solid beads such ascharcoal, alumina, asbestos and the like. The reduction may be conductedin the presence of a solvent such as dioxane, acetic acid, ethylacetate, THF, alcohol such as methanol, ethanol and the like or mixturesthereof. A pressure between atmospheric pressure to 60 psi may be used.The reaction may be carried out at a temperature from 25 to 60° C.,preferably at room temperature. The reaction time ranges from 2 to 48 h.The reduction may also be carried out by employing metal in mineralacids such Sn/HCl, Fe/HCl, Zn/HCl, Zn/CH₃CO₂H and the like.

[0235] The conversion of compound of formula (VI) to compound of formula(VII) may be carried out with an alkylchloroformate such asmethychloroformate, ethylchloroformate, propylchloroformate,benzylchloroformate and the like. The solvent of the reaction may beselected from water, acetone, tetrahydrofuran (THF), acetonitrile,dichloromethane (DCM) and the like or mixtures thereof. The reaction maybe carried out in the presence of base such as K₂CO₃, Na₂CO₃, NaOH, KOH,triethylamine and the like. The temperature of the reaction may becarried out in the presence of 0 to 60° C., preferably at 0° C. to roomtemperature. The time of the reaction is maintained in the range of1-12h, preferably in the range of 1-4 h.

[0236] In still another embodiment of the present invention there isprovided a novel intermediate of formula (VI)

[0237] where R² and R³, which may be the same or different, are eachindependently hydrogen, halogen, (C₁-C₁₀)alkyl, halogenated(C₁-C₁₀)alkyl, cyano, nitro, SR^(a), NR^(a), or OR^(a), in which R^(a)is hydrogen, (C₁-C₁₀)alkyl or halogenated (C₁-C₁₀)alkyl;

[0238] is a heterocyclic moiety in which

[0239] is a 5-membered heterocyclic skeleton, Z represents O, S, ═CH,—CH₂ or NR^(b), where R^(b) is hydrogen or a moiety, which may besubstituted or unsubstituted, straight chain or branched, selected fromthe group consisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl,(C₃-C₈)cycloalkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkylamino, amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl,aryloxy, (C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀)alkoxycarbonyl andaryloxycarbonyl;

[0240] Y¹ represents ═O or ═S group and Y² and Y³ independentlyrepresent hydrogen, halogen, cyano, nitro, formyl, hydroxy, amino, ═O,═S group or substituted or unsubstituted groups selected from(C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀) alkylhydroxy,(C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyl,(C₁-C₁₀)alkoxycarbonyl, arylcarbonyl, carboxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylsulfonyl, (C₁-C₁₀)alkylcarbony(C₁-C₁₀)alkyl,arylcarbonylamino(C₁-C₁₀)alkyl, (C₁-C₁₀) alkylcarbonyloxy(C₁-C₁₀)alkyl,amino(C₁-C₁₀)alkyl, mono(C₁-C₁₀)alkylamino, di(C₁-C₁₀)alkylamino,arylamino, (C₁-C₁₀)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl or heterocycloalkyl; Y² and Y³ when presenton adjacent carbon atoms together may also form a substituted orunsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure,optionally containing one or two hetero atoms selected from oxygen,sulfur or nitrogen.

[0241] The novel intermediate of formula (VI) may be prepared by aprocess, which comprises:

[0242] (i) reacting a compound of formula (III)

[0243] where all the symbols are as defined earlier, with a compound offormula (IV)

[0244] where L represents a leaving group such as halogen atom,(C₁-C₁₀)alkoxy group such as methoxy, ethoxy, propoxy and the like, orsulphonyl group such as methylsulfonyl, ethylsulfonyl, p-toluenesulfonyland the like; R² and R³ are as defined earlier, to produce a compound offormula (V)

[0245] where Y¹, Y², Y³, R², R³ and Z are as defined earlier, and

[0246] (ii) reducing the compound of formula (V) to produce a compoundof formula (VI)

[0247] where Y¹, Y², Y³, R², R³ and Z are as defined earlier,

[0248] The reaction of a compound of formula (III) with a compound offormula (IV) to produce a compound of formula (V) may be carried outusing a base such as KOH, NaOH, K₂CO₃, Na₂CO₃, NaH, KH, triethylamine,diisopropylethyl amine and the like. The reaction may be carried outusing a solvent such as DMSO, DMF, THF, acetonitrile, chloroform and thelike or mixtures thereof. The reaction may be carried out in inertatmosphere, which may be maintained using inert gases such as N₂ or Ar.The reaction may be carried out at a temperature in the range of 20°C.-100° C., preferably at a temperature in the range of ambient-80° C.The reaction time may range from 1 to 15 h, preferably from 6 to 12 h.

[0249] The reduction of a compound of formula (V) to produce a compoundof formula (VI) may be carried out in the presence of gaseous hydrogenand a catalyst such as Ru, Pd, Rh, Pt, Ni on solid beads such ascharcoal, alumina, asbestos and the like. The reduction may be conductedin the presence of a solvent such as dioxane, acetic acid, ethylacetate, THF, alcohol such as methanol, ethanol and the like or mixturesthereof. A pressure between atmospheric pressure to 60 psi may be used.The reaction may be carried out at a temperature from 25 to 60° C.,preferably at room temperature. The reaction time ranges from 2 to 48 h.The reduction may also be carried out by employing metal in mineralacids such Sn/HCl, Fe/HCl, Zn/HCl, Zn/CH₃CO₂H and the like.

[0250] In yet another embodiment of the present invention there isprovided a novel intermediate of formula (X)

[0251] where R¹ is halo, azido, isothiocyano, thioalcohol, —OR⁴, —NHR⁴or —N(R⁴)², where R⁴ represents hydrogen atom, or substituted orunsubstituted groups selected from (C₁-C₁₀) alkyl, (C₁-C₁₀)acyl,thio(C₁-C₁₀)acyl, —C(═O)—(C₁-C₁₀)alkoxy, —C(═S)—(C₃-C₈)cycloalkoxy,—C(═O)—(C₂-C₁₀)alkenyloxy, —C(═O)—(C₂-C₁₀)alkenyl, —C(═O)-aryloxy,—C(═S)—(C₁-C₁₀)alkoxy, —C(═S)—(C₂-C₁₀)alkenyloxy, —C(═S)-aryloxy,—C(═O)—C(═O)—(C₁-C₁₀)alkyl, —C(═O)—C(═O)-aryl,—C(═O)—C(═O)—(C₁-C₁₀)alkoxy, —C(═O)—C(═O)-aryloxy,—(C═S)—S—(C₁-C₁₀)alkyl, —(C═S)—NH₂, —(C═S)—NH—(C₁-C₁₀)alkyl,—C(═S)—N—((C₁-C₁₀)alkyl)₂, —C(═S)—NH—(C₂-C₁₀)alkenyl,(C═S)—(C═O)—(C₁-C₁₀)alkoxy, —(C═S)—(C═O)-aryloxy,—C(═S)—O—(C═O)—(C₁-C₁₀)alkyl, C(═S)—C(═S)—(C₁-C₁₀)alkyl,—C(═S)—C(═S)-aryl, thiomorpholinyl-C(═S)— or pyrrolidinyl-C(═S)—;

[0252] R² and R³, which may be the same or different, are eachindependently hydrogen, halogen, (C₁-C₁₀)alkyl, halogenated(C₁-C₁₀)alkyl, cyano, nitro, SR^(a), NR^(a), or OR^(a), in which R^(a)is hydrogen, (C₁-C₁₀)alkyl or halogenated (C₁-C₁₀)alkyl;

[0253] is a heterocyclic moiety in which

[0254] is a 5-membered heterocyclic skeleton, Z represents O, S, ═CH,—CH₂ or NR^(b) where R^(b) is hydrogen or a moiety, which may besubstituted or unsubstituted, straight chain or branched, selected fromthe group consisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl,(C₃-C₈)cycloalkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkylamino, amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl,aryloxy, (C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀)alkoxycarbonyl andaryloxycarbonyl;

[0255] Y¹ represents ═O or ═S group and Y² and Y³ independentlyrepresent hydrogen, halogen, cyano, nitro, formyl, hydroxy, amino, ═O,═S group or substituted or unsubstituted groups selected from(C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyl,(C₁-C₁₀)alkoxycarbonyl, arylcarbonyl, carboxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylsulfonyl, (C₁-C₁₀)alkylcarbony(C₁-C₁₀)alkyl,arylcarbonylamino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyloxy (C₁-C₁₀)alkyl,amino(C₁-C₁₀)alkyl, mono(C₁-C₁₀)alkylamino, di(C₁-C₁₀)alkylamino,arylamino, (C₁-C₁₀)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl or heterocycloalkyl; Y² and Y³ when presenton adjacent carbon atoms together may also form a substituted orunsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure,optionally containing one or two hetero atoms selected from oxygen,nitrogen or sulfur.

[0256] The novel intermediate of formula (X) may be prepared by aprocess, which comprises:

[0257] (i) reacting a compound of formula (III)

[0258] where all the symbols are as defined earlier, with a compound offormula (IV)

[0259] where L represents a leaving group such as halogen atom,(C₁-C₁₀)alkoxy, such as methoxy, ethoxy, propoxy and the like orsulfonyl groups such as methylsulfonyl, ethylsulfonyl, p-toluenesulfonyland the like; R² and R³ are as defined earlier, to produce a compound offormula (V)

[0260] where Y¹, Y², Y³, R², R³ and Z are as defined earlier,

[0261] (ii) reducing the compound of formula (V) to produce a compoundof formula (VI)

[0262] where Y₁, Y², Y³, R², R³ and Z are as defined earlier, and

[0263] (iii) reacting the compound of formula (VI) with a compound offormula (IX)

[0264] where R¹ represents —NHR⁴ or —N(R⁴)₂, where R⁴ representshydrogen atom, or substituted or unsubstituted groups selected from(C₁-C₁₀)alkyl, (C₁-C₁₀)acyl, thio(C₁-C₁₀)acyl, —C(═O)—(C₁-C₁₀)alkoxy,—C(═S)—(C₃-C₈)cycloalkoxy, —C(═O)—(C₂-C₁₀)alkenyloxy,—C(═O)—(C₂-C₁₀)alkenyl, —C(═O)-aryloxy, —C(═S)—(C₁-C₁₀)alkoxy,—C(═S)—(C₂-C₁₀)alkenyloxy, —C(═S)—aryloxy, —C(═O)—C(═O)—(C₁-C₁₀)alkyl,—C(═O)—C(═O)-aryl, —C(═O)—C(═O)—(C₁-C₁₀)alkoxy, —C(═O)—C(═O)-aryloxy,—(C═S)—S—(C₁-C₁₀)alkyl, —(C═S)—NH₂, —(C═S)—NH—(C₁-C₁₀)alkyl,—C(═S)—N—((C₁-C₁₀)alkyl)₂, —C(═S)—NH—(C₂-C₁₀)alkenyl,(C═S)—(C═O)—(C₁-C₁₀)alkoxy, —(C═S)—(C═O)-aryloxy,—C(═S)—O—(C═O)—(C₁-C₁₀)alkyl, C(═S)—C(═S)—(C₁-C₁₀)alkyl,—C(═S)—C(═S)-aryl, thiomorpholinyl-C(═S)— or pyrrolidinyl-C(═S)—, toproduce a compound of formula (X)

[0265] where Y¹, Y², Y³, R², R³ and Z are as defined above.

[0266] The reaction of a compound of formula (III) with a compound offormula (IV) to produce a compound of formula (V) may be carried outusing a base such as KOH, NaOH, K₂CO₃, Na₂CO₃, NaH, KH, triethylamine,diisopropylethyl amine and the like. The reaction may be carried outusing a solvent such as DMSO, DMF, THF, acetonitrile, chloroform and thelike or mixtures thereof. The reaction may be carried out in inertatmosphere, which may be maintained using inert gases such as N₂ or Ar.The reaction may be carried out at a temperature in the range of 20 to100° C., preferably at a temperature in the range of ambient to 80° C.The reaction time may range from 1 to 15 h, preferably from 6 to 12 h.

[0267] The reduction of a compound of formula (V) to produce a compoundof formula (VI) may be carried out in the presence of gaseous hydrogenand a catalyst such as Ru, Pd, Rh, Pt, Ni on solid beads such ascharcoal, alumina, asbestos and the like. The reduction may be conductedin the presence of a solvent such as dioxane, acetic acid, ethylacetate, THF, alcohol such as methanol, ethanol and the like or mixturesthereof. A pressure between atmospheric pressure to 60 psi may be used.The reaction may be carried out at a temperature from 25 to 60° C.,preferably at room temperature. The reaction time ranges from 2 to 48 h.The reduction may also be carried out by employing metal in mineralacids such Sn/HCl, Fe/HCl, Zn/HCl, Zn/CH₃CO₂H and the like.

[0268] The reaction of a compound of formula (VI) defined above with acompound of formula (IX) defined above to produce a compound of formula(X) may be carried out in the presence or absence of a base such asK₂CO₃, NaH, t-BuOK and the like or mixtures thereof. The reaction may becarried out in the presence of a solvent such as toluene, DMF, THF, oracetonitrile. The reaction may also be carried out in the presence ofLewis acids such as BF₃.OEt₂, ZnCl₂, Ti(OiPr)₄, lanthanide metalcomplexes and the like in the presence of DCE, DMF, THF or the like ormixtures thereof. The reaction temperature may be in the range of 0 to120° C., preferably at a temperature in the range of 0 to 100° C. Thereaction time may range from 3 to 24 h, preferably from 4 to 12 h.

[0269] In yet another embodiment of the present invention there isprovided a novel intermediate of formula (XVI)

[0270] where R^(c) represents (C₁-C₁₀)alkyl group such as methyl, ethyl,propyl, and the like, or aralkyl such as benzyl, allyl group and thelike; R² and R³, which may be the same or different, are eachindependently hydrogen, halogen, (C₁-C₁₀)alkyl, halogenated(C₁-C₁₀)alkyl, cyano, nitro, SR^(a), NR^(a), or OR^(a), in which R^(a)is hydrogen, (C₁-C₁₀)alkyl or halogenated (C₁-C₁₀)alkyl;

[0271] is a heterocyclic moiety in which

[0272] is a 5-membered heterocyclic skeleton, Z represents O, S, ═CH,—CH₂ or NR^(b), where R^(b) is hydrogen or a moiety, which may besubstituted or unsubstituted, straight chain or branched, selected fromthe group consisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl,(C₃-C₈)cycloalkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkylamino, amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl,aryloxy, (C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀)alkoxycarbonyl andaryloxycarbonyl;

[0273] Y¹ represents ═O or ═S group and Y² and Y³ independentlyrepresent hydrogen, halogen, cyano, nitro, formyl, hydroxy, amino, ═O,═S group or substituted or unsubstituted groups selected from(C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyl,(C₁-C₁₀)alkoxycarbonyl, arylcarbonyl, carboxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylsulfonyl, (C₁-C₁₀)alkylcarbony(C₁-C₁₀)alkyl,arylcarbonylamino(C_(1-C) ₁₀)alkyl,(C₁-C₁₀)alkylcarbonyloxy(C₁-C₁₀)alkyl, amino(C₁-C₁₀)alkyl,mono(C₁-C₁₀)alkylamino, di(C₁-C₁₀)alkylamino, arylamino, (C_(1-C)₁₀)alkoxy, aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl,heterocyclyl or heterocycloalkyl; Y² and Y³ when present on adjacentcarbon atoms together may also form a substituted or unsubstituted 5 or6 membered aromatic or non-aromatic cyclic structure, optionallycontaining one or two hetero atoms selected from oxygen, sulfur ornitrogen.

[0274] The novel intermediate of formula (XVI) may be prepared by aprocess, which comprises:

[0275] (i) reacting a compound of formula (VII)

[0276] where all the symbols are as defined earlier, with a compound offormula (XIV)

[0277] where L represents a leaving group such as halogen atom,(C₁-C₁₀)alkoxy group such as methoxy, ethoxy, propoxy and the like, orsulphonyl group such as methylsulfonyl, ethylsulfonyl, p-toluenesulfonyland the like; to produce a compound of formula (XV)

[0278] where R^(c), Y¹, Y², Y³, R², R¹ and Z are as defined earlier and

[0279] (ii) hydrolysing the acetonide moiety in the compound of formula(XV) using conventional methods to produce a compound of formula (XVI)

[0280] where R^(c), Y¹, Y², Y³, R², R³ and Z are as defined earlier.

[0281] The reaction of a compound of formula (VII) with a compound offormula (XIV) to produce a compound of formula (XV) may be carried outin the presence of a base. The base employed may be selected from K₂CO₃,NaH, t-BuOK, LDA and the like. The reaction may be carried out in thepresence of a solvent such as DMF, THF, DMSO, methanol, ethanol,propanol and the like. The reaction may be carried at a temperature inthe range of −78 to 120° C., preferably at a temperature in the range of−78 to 100°C. The reaction time may range from 2 to 24 h, preferablyfrom 2 to 20 h.

[0282] The hydrolysis of a compound of formula (XV) to produce acompound of formula (XVI) may be carried out using dilute mineral acidsuch as HCl, H₂SO₄ and the like, organic acids such as aqueous aceticacid, p-toluene sulfonic acid, camphor sulfonic acid, trifluoro aceticacid and the like. The reaction may be carried out in the presence ofsuitable solvent such as water, methanol, ethanol, propanol, THF,dioxane and the like or mixtures thereof. The reaction may be carried ata temperature in the range of 30 to 100° C., preferably at a temperaturein the range of 30 to 60° C. The reaction time may range from 10 min to5 h, preferably from 30 min to 2.5 h.

[0283] In yet another embodiment of the present invention there isprovided a novel intermediate of formula (XVIII)

[0284] wherein R^(c) represents (C₁-C₁₀)alkyl group such as methyl,ethyl, propyl, and the like or aralkyl such as benzyl, allyl group andthe like; R² and R³, which may be the same or different, are eachindependently hydrogen, halogen, (C₁-C₁₀)alkyl, halogenated(C₁-C₁₀)alkyl, cyano, nitro, SR^(a), NR^(a), or OR^(a), in which R^(a)is hydrogen (C₁-C₁₀)alkyl or halogenated (C₁-C₁₀)alkyl;

[0285] is a heterocyclic moiety in which

[0286] is a 5-membered heterocyclic skeleton, Z represents O, S, ═CH,—CH₂ or NR^(b), where R^(b) is hydrogen or a moiety, which may besubstituted or unsubstituted, straight chain or branched, selected fromthe group consisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl,(C₃-C₈)cycloalkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkylamino, amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl,aryloxy, (C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀)alkoxycarbonyl andaryloxycarbonyl;

[0287] Y¹ represents ═O or ═S group and Y² and Y³ independentlyrepresent hydrogen, halogen, cyano, nitro, formyl, hydroxy, amino, ═O,═S group or substituted or unsubstituted groups selected from(C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyl,(C₁-C₁₀)alkoxycarbonyl, arylcarbonyl, carboxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylsulfonyl, (C₁-C₁₀)alkylcarbony(C₁-C₁₀)alkyl,arylcarbonylamino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyloxy (C₁-C₁₀)alkyl,amino(C₁-C₁₀)alkyl, mono(C₁-C₁₀)alkylamino, di(C₁-C₁₀)alkylamino,arylamino, (C₁-C₁₀)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl or heterocycloalkyl; Y² and Y³ when presenton adjacent carbon atoms together may also form a substituted orunsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure,optionally containing one or two hetero atoms.

[0288] The novel intermediate of formula (XVIII) may be prepared by aprocess, which comprises: reacting a compound of formula (VII)

[0289] where all the symbols are as defined earlier, with a compound offormula (XVII)

[0290] where L represents a leaving group such as halogen atom(C₁-C₁₀)alkoxy group such as methoxy, ethoxy, propoxy and the like, orsulphonyl group such as methylsulfonyl, ethylsulfonyl, p-toluenesulfonyland the like; produce a compound of formula (XVIII)

[0291] where R^(c), Y¹, Y², Y³, R², R³ and Z are as defined earlier.

[0292] The reaction of a compound of formula (VII) defined above with acompound of formula (XVII) defined above may be carried out in thepresence of a base such as NaH, NaOMe, K₂CO₃, n-BuLi, LDA and the like.The reaction may be carried out in the presence of a solvent such asDMF, THF, DMSO, benzene and the like or mixtures thereof. The reactionmay be carried out at a temperature in the range of −78 to 70° C.preferably at a temperature in the range of −78 to 50° C. The reactiontime may range from 1 to 15 h preferably 1 to 10 h.

[0293] It is appreciated that in any of the above-mentioned reactions,any reactive group in the substrate molecule may be protected accordingto conventional chemical practice. Suitable protecting groups in any ofthe above mentioned reactions are tertiarybutyldimethylsilyl,methoxymethyl, triphenyl methyl, benzyloxycarbonyl, tetrahydropyran(THP)etc, to protect hydroxyl or phenolic hydroxy group;N-tert-butoxycarbonyl (N-Boc), N-benzyloxycarbonyl (N-Cbz),N-9-fluorenyl methoxy carbonyl (—N-FMOC), benzophenoneimine,propargyloxy carbonyl (POC) etc, for protection of amino or anilinogroup, acetal protection for aldehyde, ketal protection for ketone andthe like. The methods of formation and removal of such protecting groupsare those conventional methods appropriate to the molecule beingprotected.

[0294] The compounds of this invention may be optically active. Thecompounds of this invention may be racemic mixtures or tautomers.

[0295] The stereoisomers includes enatiomers and geometrical isomerssuch as (R), (S), a mixture of (R) and (S), (E), (Z) or a mixture of (E)and (Z), may be prepared by using reactants in such a way to obtainsingle isomeric form in the process wherever applicable or by conductingthe reaction in the presence of reagents or catalysts in their singleenantiomeric form. The single enantiomer, wherever applicable, may beprepared by resolving the racemic mixture by conventional methods. Thestereoisomers of the compounds forming part of this invention may beprepared by using reactants in their single enantiomeric form in theprocess wherever possible or by conducting the reaction in the presenceof reagents or catalysts in their single enantiomer form or by resolvingthe mixture of stereoisomers by conventional methods. Some of thepreferred methods include use of microbial resolution, resolving thediastereomeric salts formed with chiral acids such as mandelic acid,camphorsulfonic acid, tartaric acid, lactic acid, and the like whereverapplicable or chiral bases such as brucine, cinchona alkaloids and theirderivatives and the like. Commonly used methods are compiled by Jaqueset al in “Enantiomers, Racemates and Resolution” (Wiley Interscience,1981). Where appropriate the compounds of formula (I) may be resolved bytreating with chiral amines, aminoacids, aminoalcohols derived fromaminoacids; conventional reaction conditions may be employed to convertacid into an amide; the diastereomers may be separated either byfractional crystallization or chromatography and the stereoisomers ofcompound of formula (I) may be prepared by hydrolyzing the purediastereomeric amide.

[0296] The prodrugs such as esters and amides of the compounds offormula (I) can be prepared by conventional methods.

[0297] The metabolites, which are formed inside the body of the mammalare formed by the reaction of various enzymes present in the body withthe compounds of formula (I).

[0298] The invention includes in vivo hydrolysable precursors of thecompounds of formula (I). The hydrolysable precursors of the compoundsof formula (I) may be esters.

[0299] The pharmaceutically acceptable salts are prepared by reactingthe compounds of formula (I) wherever applicable with 1 to 4 equivalentsof a base such as sodium hydroxide, sodium methoxide, sodium hydride,potassium t-butoxide, calcium hydroxide, magnesium hydroxide and thelike, in solvent like ether, THF, methanol, t-butanol, dioxane,isopropanol, ethanol and the like. Mixture of solvents may be used.Organic bases like lysine, arginine, diethanolamine, choline,tromethamine, guanidine and their derivatives etc. may also be used.Alternatively, acid addition salts wherever applicable are prepared bytreatment with acids such as hydrochloric acid, hydrobromic acid, nitricacid, sulfuric acid, phosphoric acid, p-toluenesulphonic acid,methanesulfonic acid, acetic acid, citric acid, maleic acid salicylicacid, hydroxynaphthoic acid, ascorbic acid, palmitic acid, succinicacid, benzoic acid, benzenesulfonic acid, tartaric acid and the like insolvents like ethyl acetate, ether, alcohols, acetone, THF, dioxane etc.Mixture of solvents may also be used. The salts of amino acid groups andother groups may be prepared by reacting the compounds of formula (I)with the respective groups in solvent like alcohols, ketones, ether andthe like. Mixture of solvents may be used.

[0300] Various polymorphs of a compound of general formula (I) formingpart of this invention may be prepared by crystallization of compound offormula (I) under different conditions. For example, using differentsolvents commonly used or their mixtures for recrystallization;crystallizations at different temperatures; various modes of cooling,ranging from very fast to very slow cooling during crystallizations.Heating or melting the compound followed by gradual or fast cooling mayalso obtain polymorphs. The presence of polymorphs may be determined bysolid probe nmr spectroscopy, IR spectroscopy, differential scanningcalorimetry, powder X-ray diffraction or such other techniques.

[0301] The present invention also provides pharmaceutical compositions,containing compounds of the general formula (I), as defined above, theirderivatives, their analogs, their tautomeric forms, their stereoisomers,their polymorphs, their pharmaceutically acceptable salts, theirprodrugs, their metabolites, or their pharmaceutically acceptablesolvates in combination with the usual pharmaceutically employedcarriers, diluents and the like. The present invention also providespharmaceutical compositions made using compounds of the general formula(I) as defined above, their stereoisomers, their polymorphs, or theirpharmaceutically salts in combination with the usual pharmaceuticallyemployed carriers, diluents and the like. The pharmaceuticalcompositions according to this invention can be used for the preventionor treatment of bacterial infections. They can also be used for theprevention or treatment of bacterial infections associated withmultidrug resistance.

[0302] Pharmaceutically acceptable solvates of compound of formula (I)forming part of this invention may be prepared by conventional methodssuch as dissolving the compounds of formula (I) in solvents such aswater, methanol, ethanol etc., preferably water and recrystallizing byusing different crystallization techniques.

[0303] The pharmaceutical compositions may be in the forms normallyemployed, such as tablets, capsules, powders, syrups, solutions,suspensions and the like, may contain flavorants, sweeteners etc. insuitable solid or liquid carriers or diluents, or in suitable sterilemedia to form injectable solutions or suspensions. Such compositionstypically contain from 0.5 to 20%, preferably 0.5 to 10% by weight ofactive compound, the remainder of the composition being pharmaceuticallyacceptable carriers, diluents or solvents.

[0304] Suitable pharmaceutically acceptable carriers include solidfillers or diluents and sterile aqueous or organic solutions. The activecompounds will be present in such pharmaceutical compositions in theamounts sufficient to provide the desired dosage in the range asdescribed above. Thus, for oral administration, the compounds can becombined with a suitable solid, liquid carrier or diluent to formcapsules, tablets, powders, syrups, solutions, suspensions and the like.The pharmaceutical compositions, may, if desired, contain additionalcomponents such as flavorants, sweeteners, excipients and the like. Forparenteral administration, the compounds can be combined with sterileaqueous or organic media to form injectable solutions or suspensions.For example, solutions in sesame or peanut oil, aqueous propylene glycoland the like can be used, as well as aqueous solutions of water-solublepharmaceutically-acceptable acid addition salts or salts with base ofthe compounds. The injectable solutions prepared in this manner can thenbe administered intravenously, intraperitoneally, subcutaneously, orintramuscularly, with intramuscular administration being preferred in^(mans.)

[0305] A method of treating or preventing an infectious disorder in asubject is provided by administering an effective amount ofoxazolidinone as disclosed herein to the subject, wherein the infectiousdisorder is characterized by the presence of microbial infection causedby pathogens such as Gram-positive, Gram-negative, aerobic and anerobicbacteria such as Methicillin-Resistant Staphylococcus Aureas (MRSA),Pseudomonas aeruginosa, Escherischia spp., Streptococci including Str.pneumoniae, Str. pyogenes, Enterococci as well as anaerobic organismssuch as Bacteroides spp., Clostridia spp. species and Acid-fastorganisms such as Mycobacterium tuberculosis, Mycobacterium avium andMycobacterium spp. Fastidious Gram negative organisms, Hemophilusinfluenzae (H. influenzae), Morexella catarrhalis (M. catarrhalis) andseveral other bacteria resistant to fluoroquinolone, macrolide,Vancomycin, aminoglycosides, Streptogramin, Lincosamides and β lactamresistant species. Such disorders include infections of the middle,internal and external ear including otitis media, infections of thecranial sinuses, eye infections, infections of the oral cavity, centralnervous system infections, infections of teeth and gums, infections ofthe mucosa, respiratory tract infections, genitourinary tractinfections, gastro-intestinal infections, septicemia, bone and jointinfections, skin and soft infections, bacterial endocarditis, burns,nosocomical infections, pre- and postsurgical infections, opportunisticinfections in the immune compromised, intracellular infections such asChlamydia and Mycoplasma. A method of preventing an infectious disorderin a subject who is at risk for developing an infectious disorder isprovided by administering to the subject an amount of an oxazolidinoneas disclosed herein sufficient to prevent the infectious disorders.Examples of a subject who is at risk for developing an infectiousdisorder are, but are not limited to, a subject who has or will undergoa surgical procedure, will be hospitalized, a health care worker orprovider, a person who will be exposed to another who has an infectiousdisorder and the like. A method for treating or preventing an infectiousdisorder may result from inhibiting the growth of bacteria or killingthe bacteria.

[0306] In addition to the compounds of formula (I) the pharmaceuticalcompositions of the present invention may also contain or beco-administered with one or more known drugs selected from otherclinically useful antibacterial agents such as β-lactams,aminoglycosides, other oxazolidinones, such as linezolid,fluoroquinolines, macrolides or any other suitable antiinfective agent.These may include penicillins such as oxacillin or flucloxacillin andcarbapenems such as meropenem or imiphenem to broaden the therapeuticeffectiveness against, for example, methicillin-resistant staphylococci.Compounds of the formula (I) of the present invention may also containor be co-admistered with bactericidal/permeability-increasing proteinproduct (BPI) or efflux pump inhibitors to improve activity against gramnegative bacteria and bacteria resistant to antimicrobial agents.

[0307] The compounds of the formula (I), as defined above are clinicallyadministered to mammals, including human beings, via either oral,rectal, vaginal, topical or parenteral routes. Administration by theoral route is preferred, being more convenient and avoiding the possiblepain and irritation of injection. However, in circumstances where thepatient cannot swallow the medication, or absorption following oraladministration is impaired, as by disease or other abnormality, it isessential that the drug be administered accordingly by an alternateroute. By either oral or parenteral route, the dosage is in the range ofabout 0.5 mg/kg to about 50 mg/kg body weight of the subject per dayadministered singly or as divided doses 1-4 times/day. However, theoptimum dosage for the individual subject being treated will bedetermined by the person responsible for treatment, generally smallerdoses being administered initially and thereafter increments made todetermine the most suitable dosage. The amount(s) that is administeredshould be effective to elicit the biological or medical response sought.

[0308] The invention is explained in detail in the examples given belowwhich are provided by way of illustration only and therefore should notbe construed to limit the scope of the invention.

General Procedure for the Preparations 1-12

[0309] A mixture of appropriate nitro compound such as4-fluoronitrobenzene and the like, a five membered heterocyclic group,containing two heteroatoms selected from oxygen, nitrogen or sulflur,and is substituted by an ═O or ═S group, the heterocycle may also befused with substituted or unsubstituted phenyl group, (1.1 eq) andanhydrous K₂CO₃ (2.0 eq) in dry DMF was stirred at temperature rangingfrom 0 to 100° C. (depending on the substrate) overnight. Cold water wasadded to the reaction mixture and the solid formed was filtered. Thefiltered solids were dried to yield pure compound. Yield: 50-85%.

REPRESENTATIVE PREPARATIONS Preparation 11-(2-Fluoro-4-nitrophenyl)-4-imidazolidinone

[0310]

[0311] A solution of 4-imidazolidinone (9.5 g, 110.5 mmol), 3,4-difluoronitrobenzene (12.2 ml, 110.5 mmol) and diisopropyl ethylamine (28.6 ml,165 mmol) in dry DMF (80 ml) was heated to 60° C. overnight under argon.The reaction mixture was allowed to cool to room temperature and icepieces were added. The solid formed was filtered and washed with water.The solid was dried under air to yield the nitro compound (19.5 g,78.5%) as yellow crystals.

[0312]¹H NMR (DMSO, 200 MHz): δ 8.81 (bs, 1H), 8.07-7.96 (m, 2H), 6.82(t, J=8.8 Hz, 1H), 4.97 (s, 2H), 4.06 (s, 2H). Mass (CI method): 226,185, 152.

Preparation 2 1-(4-Nitrophenyl)-4-imidazolidinone

[0313]

[0314] A solution of 4-imidazolidinone (9.5 g, 110.5 mmol),4-nitrobenzene (1 eq) and diisopropyl ethylamine (28.6 mL, 165 mmol) indry DMF (80 mL) was heated to 60° C. overnight under argon. The reactionmixture was allowed to cool to room temperature and ice pieces wereadded. The solid formed was filtered and washed with water. The solidwas air dried to yield the nitro compound as yellow crystals.

[0315]¹H NMR (DMSO-d⁶, 200 MHz): δ 8.83 (bs, 1H), 8.13 (d, J=8.8 Hz,2H), 6.70 (d, J=8.8 Hz, 2H), 4.82 (s, 2H), 3.92 (s, 2H); Mass (CImethod): 208, 167; IR (KBr, cm⁻¹): 1709, 1602, 1308.

Preparation 3 1-(2,6-Difluoro-4-nitrophenyl)-4-imidazolidinone

[0316]

[0317] A solution of 4-imidazolidinone (9.5 g, 110.5 mmol),3,4,5-trifluoronitrobenzene (1 eq) and diisopropyl ethylamine (28.6 mL,165 mmol) in dry DMF (80 mL) was heated to 60° C. overnight under argon.The reaction mixture was allowed to cool to room temperature and icepieces were added. The solid formed was filtered and washed with water.The solid was air dried to yield the nitro compound as yellow crystals.

[0318]¹H NMR (DMSO-d⁶, 200 MHz): δ 8.76 (s, 1H), 7.97 (dd, J=2.6 Hz &7.0 Hz, 2H), 5.1 (s, 2H), 4.2 (s, 2H); Mass (CI method): 244, 187; IR(KBr, cm−1): 3188, 3063, 2360, 1715, 1609, 1514, 1449, 1398, 1293, 1157.

[0319] Similarly preparations 4-12 have been prepared by a personskilled in the art according to the methodology as described inpreparations 1-3 S. No. Preparation Analystical data 4

1HNMR (CDCl3, 200MHz): δ 8.25(d, J=9.2Hz, 2H), 7.72(d, J=9.2Hz, 2H),4.57(t, J=7.3Hz, 2H), 4.18(t, J=7.3Hz, 2H). Mass (CI method): 209. 5

1HNMR (CDCl3, 200MHz): δ 8.12-7.93(m, 3H), 4.56(t, J=7.3Hz, 2H), 4.23(t,J=7.3Hz, 2H). Mass (CI method): 227. 6

1HNMR (CDCl3, 200MHz): δ 7.92(d, J=7.8Hz, 2H), 4.64(t, J=7.4Hz, 2H),4.07(t, J=7.4Hz, 2H). Mass (CI method): 245, 215. 7

1HNMR (CDCl3, 200MHz): δ 8.00(m, 1H), 7.15(m, 2H), 4.56(t, J=7.4Hz, 2H),4.06(t, J=7.4Hz, 2H). Mass (CI method): 226, 180, 164, 152, 135, 109,94. 8

1HNMR (CDCl3, 200MHz): δ 8.64-8.48(m, 2H), 7.69(d, J=8.8Hz, 1H), 4.60(t,J=7.3Hz, 2H), 4.01(t, J=7.3Hz, 2H). Mass (CI method): 276, 232, 217,171, 144. 9

1HNMR (CDCl3, 200MHz): δ 8.14-8.04(m, 2H), 7.90(t, J=7.6Hz, 1H), 4.76(t,J=8.4Hz, 2H), 4.23(t, J=8.4Hz, 2H). Mass (CI method): 242, 223, 167,121, 94. 10

1HNMR (CDCl3, 200MHz): δ 8.14-8.07(m, 2H), 7.72(t, J=7.6Hz, 1H), 4.43(t,J=7.6Hz, 2H), 3.57(t, J=7.6Hz, 2H). Mass (CI method): 258, 239, 212,193, 108. 11

1HNMR (CDCl3, 200MHz): δ 8.11-8.02(m, 2H), 7.96(t, J=7.8Hz, 1H),4.09-3.83(2t, 4H), 3.27(s, 2H). Mass (CI method): 255, 236, 209, 190. 12

1HNMR (CDCl3, 200MHz): δ 8.23(m, 2H), 7.81(t, J=7.4Hz, 1H), 7.22(t,J=7.4Hz, 1H), 7.03(d, J=8.4Hz, 1H). Mass (CI method): 288, 258, 243,197, 94.

Preparation 13 N1-(2-aminoethyl)-4-nitroaniline

[0320]

[0321] A solution of 4-fluoronitrobenzene (5 g, 35.4 mmol) in CH3CN (250ml) was at room temperature under argon overnight. The reaction mixturewas filtered and the was concentrated. The residue obtained wassuspended in pet. ether and filtered. The ere collected to afford thenitro compound (4.1 g, 64%) as yellow crystals.

[0322]¹H NMR (DMSO+CDCl₃, 200 MHz): δ 7.97 (d, J=9.3 Hz, 2H), 7.09 (bs,1H), 6.62 (d, J=9.3 Hz, 2H), 2.80-3.40 (m, 6H). Mass(CI method): 181,152, 135, 105.

Preparation 14

[0323] 1-(4—Nitrophenyl)-2-imidazolidinone

[0324] A solution of phosgene (20% in toluene, 13 ml, 26.5 mmol) intoluene was added drop wise to a solution of the diamine (4 g, 22 mmol)(obtained in preparation 13) and Et₃N (7.6 ml, 55 mmol) indichloromethane (100 ml) at 0° C. under argon. After being stirred atsame temperature for 1 h, the reaction mixture was poured in water andextracted with dichloromethane (4×150 ml). The combined organic extractswere washed with water, brine and dried. The residue obtained uponevaporation of the solvents was passed through a column of silica gel toafford the product (3 g, 66%) as yellow solid.

[0325]¹H NMR (CDCl₃, 200 MHz): δ 8.17 (d, J=9.3 Hz, 2H), 7.75 (d, J=9.2Hz, 2H), 7.07 (bs, 1H), 4.00 (t, J=8.8 Hz, 2H), 3.59 (t, J=8.8 Hz, 2H).Mass(CI method): 207, 151, 105.

Preparation 15 1-Methyl-3-(4-nitrophenyl)-2-imidazolidinone

[0326]

[0327] Sodium hydride (60% in oil, 138 mg, 5.3 mmol) was added portionwise to a solution of the nitro compound (1 g, 4.8 mmol) (obtained inpreparation 14) in dry DMF (15 ml) under argon at 0° C. Stirred thereaction mixture at the same temperature for 15 min. Methyl iodide (MeI)(0.68 g, 4.8 mmol) was added and the reaction mixture was stirred for 1h. Ice pieces were added to the reaction mixture and the solid formedwas filtered to afford the product (900 mg, 84%) as yellow crystals.

[0328]¹H NMR (CDCl₃, 200 MHz): δ 8.19 (d, J=9.3 Hz, 2H), 7.70 (d, J=9.3Hz, 2H), 3.88 (t, J=8.8 Hz, 2H), 3.54 (t, J=8.8 Hz, 2H), 2.93 (s, 3H).Mass(CI method): 222.

Preparation 16 N1-phenyl-2-azidoacetamide

[0329]

[0330] Chloroacetyl chloride (5.1 ml, 64.5 mmol) was added drop wise toa solution of aniline (5 g, 53.7 mmol) and Et₃N (18.7 ml, 134.3 mmol) indichloromethane (150 ml) at 0° C. under argon. After the completion ofreaction (TLC control), the reaction mixture was diluted withdichloromethane (300 ml). The resultant mixture was washed with water,brine and dried. The residue obtained upon evaporation of solvent wastaken up in dry DMF (40 ml), added NaN₃ (6.15 g, 94.6 mmol) and theresultant mixture was stirred at 80° C. for 2 h. The reaction mixturewas diluted with ethyl acetate and washed with water, brine and dried.The residue obtained upon evaporation of the solvent was chromatographedover silica gel to afford the azide (6 g, 63%).

Preparation 17 N1-phenyl-2-(2-fluoro-4-nitroanilino)acetamide

[0331]

[0332] A solution of the azide (6 g, 34 mmol) obtained in preparation16, was taken in MeOH (60 ml) and the resultant solution washydrogenated over 10% Pd on charcoal (2.5 g) overnight. The reactionmixture was filtered on a celite pad and the filtrate was concentrated.To this residue dry DMF (40 ml) was added followed by diisopropyl ethylamine (16.7 ml, 93.8 mmol) and 3,4-difluoronitro benzene (3.8 ml, 37.5mmol). The resultant solution was kept at 80° C. overnight withcontinuous monitoring by TLC. Ice-cold water was added to the reactionmixture and the solid separated was filtered to afford the nitrocompound as a yellow solid (6 g, 61%).

[0333]¹H NMR (DMSO+CDCl₃, 200 MHz): δ 9.74 (bs, 1H), 7.84-8.00 (m, 2H),7.58 (d, J=8.3 Hz, 2H), 7.30 (d, J=8.3 Hz, 2H), 7.08 (m, 1H), 6.66 (t,J=8.8 Hz, 1H), 6.45 (bs, 1H), 4.09 (d, J=5.4 Hz, 2H). Mass (CI Method):290.

Preparation 18 N1-(2-anilinoethyl)-2-fluoro-4-nitroaniline

[0334]

[0335] A 1 M solution of BH₃.THF (45 ml, 45 mmol) was added drop wise toa solution of the nitro compound (4.5 g, 15.5 mmol) (obtained inpreparation 17) in dry THF (30 ml) at 0° C. under argon. The reactionmixture was stirred overnight at room temperature and then water wasadded cautiously to quench the excess borane. The volatiles were removedfrom the reaction mixture under vacuum and the residue was taken up inethyl acetate (400 ml). The organic layer was washed with water, brineand dried. The residue obtained upon evaporation of the solvent waspassed through column to afford the product (4 g, 93%).

[0336]¹H NMR (CDCl₃, 200 MHz): δ 8.02-7.86 (m, 2H), 7.26-7.18 (m, 2H),682-6.62 (m, 4H), 4.94 (bs, 1H), 3.83 (bs, 1H), 3.51 (s, 4H). Mass (CImethod): 274.

Preparation 19 1-(2-Fluoro-4-nitrophenyl)-3-phenyl-2-imidazolidinone

[0337]

[0338] A solution of phosgene (20% in toluene, 7.4 ml, 14.7 mmol) wasadded drop wise to a solution of the diamine (4 g, 14.5 mmol) (obtainedin preparation 18) and Et3N (5.6 ml, 40.4 mmol) in dichloromethane (50ml) at 0° C. under argon. Stirred for 2 h at the same temperature thereaction mixture was diluted with dichloromethane (300 ml) and washedwith water, brine and dried. The crystals obtained upon evaporation ofthe solvents were suspended in petroleum ether and filtered. The productwas isolated as yellow crystals (4 g, 91.4%).

[0339]¹H NMR (CDCl₃, 200 MHz): δ 8.10-7.11 (m, 8H), 4.22-4.00 (m, 4H).Mass (CI Method): 302, 106.

Preparation 201-(2-Fluoro-4-nitrophenyl)-3-hydroxymethyl-4-imidazolidinone

[0340]

[0341] A mixture of nitro compound (9 g, 40 mmol) (obtained inpreparation 1) and 40% solution of formaldehyde (100 mL) was heated toreflux for 4 h. The reaction mixture was allowed to cool to roomtemperature and ice water mixture was added. The precipitated solid wasfiltered and dried to give the product as yellow solid (8.5 g, 83%yield).

[0342]¹H NMR (DMSO-d6, 200 MHz): δ 8.10-7.95 (m, 2H), 6.90-6.80 (m, 1H),6.20 (t, J=6.8 Hz, 1H), 5.13 (d, J=2.9 Hz, 2H), 4.77 (d, J=7.3 Hz, 2H),4.19 (s, 2H). Mass (CI method): 226.

Preparation 211-(2-Fluoro-4-nitro-phenyl)-3-tetrahydro-pyran-2-yloxymethyl)-imidazolidin-4-one

[0343]

[0344] A solution of nitro compound (6.7 g, 26.2 mmol) (obtained inpreparation 20), pyridinium p-toluenesulphonate (PPTS) (65 mg, 0.39mmol) and 3,4-dihydro-2H-pyran (3.6 mL, 39.4 mmol) in dichloromethane(100 mL) was stirred at room temperature under argon overnight. Thereaction mixture was diluted with dichloromethane (400 mL), washed withhalf-saturated brine (2×100 mL) and dried. The residue obtained uponevaporation of solvent was passed through a column of silica gel toafford the product as yellow solid (7 g, 79% ).

[0345]¹H NMR (CDCl3, 200 MHz): δ 8.05-7.85 (m, 2H), 6.60-6.45 (m, 1H),5.304.70 (m, 5H), 4.17 (s, 2H), 4.20-3.30 (m, 4H), 2.00-1.40 (m, 6H).Mass (CI method): 340, 256, 237.

Preparation 221-(2,6-Difluoro-4-nitrophenyl)-3-hydroxymethyl-4-imidazolidinone

[0346]

[0347] A solution of nitro compound (26 g, 106.9 mmol), obtained inpreparation 3, in formalin (37-41% w/v in water, 150 mL) was refluxedovernight. Ice water was added to the reaction mixture and the solidobtained was filtered. The dried title compound was further driedazeotropically with toluene (2×100 mL) to afford the product as a paleyellow solid (26 g, 89.3%). Mp 140-143° C.

[0348] 1H NMR (DMSO-d6, 200 MHz): δ 7.99 (dd, J=2.4 Hz & 9.8 Hz, 2H),6.22 (t, J=7.3, 1H), 5.25 (s, 2H), 4.76 (d, J=7.0, 2H), 4.35 (s, 2H);Mass (CI method): 244, 214; IR (KBr, cm⁻¹): 3438, 1721, 1519.

Preparation 23 2-(2,6-Difluoro-4-nitro-phenylamino)-acetamide

[0349]

[0350] To a stirred solution of glycinamide hydrochloride (45 g, 407mmol) in DMF (500 mL) was added successively triethylamine (197 mL, 1.43mol) followed by 3,4,5-trifluronitrobenzene (72 g, 407 mmol) at roomtemperature over 15 min. The reaction mixture was heated to 80° C.overnight and then allowed to cool to room temperature. Ice piecessuspended in water were added to the reaction mixture and the solidobtained was filtered. The solid was dried to afford title compound (62g, 67%) that was taken up directly for the next step without furtherpurification. Mp 160-162° C.

[0351]¹H NMR (DMSO-d₆, 200 MHz): δ 7.90 (dd, J=2.4 Hz & 8.1 Hz, 2H),7.47 (s, 1H), 7.13 (s, 1H), 6.87 (bs, 1H), 3.96-3.92 (m, 2H); Mass (CImethod): 232, 200; IR (KBr, cm⁻¹): 1686, 1616, 1333.

Preparation 241-(2,6-Difluoro-4-nitrophenyl)-3-hydroxymethyl-4-imidazolidinone

[0352]

[0353] A solution of nitro compound (60 g, 283 mmol), obtained inpreparation 23, in formalin (37-41% w/v in water, 180 mL) and water (700mL) was refluxed overnight. Ice water was added to the reaction mixtureand the solid obtained was filtered. The dried title compound wasfurther dried azeotropically with toluene (2×300 mL) to afford theproduct as a pale yellow solid (60 g, 96%).

Preparation 251-(2,6-Difluoro-4-nitro-phenyl)-3-(tetrahydro-pyran-2-yloxymethyl)-imidazolidin-4-one

[0354]

[0355] A solution of1-(2,6-difluoro-4-nitrophenyl)-3-hydroxymethyl-4-imidazolidinone (60 g,220.6 mmol), obtained in preparation 24, 3,4-dihydro-2H-pyran (24 mL,264.7 mmol) and pyridinium p-toluene sulfonate (5.5 g, 22 mmol) indichloromethane (500 mL) was stirred at room temperature overnight. Thereaction mixture was concentrated (100 mL) and directly loaded on acolumn of silica gel. Elution with 1:1 ethyl acetate-pet.ether gave theprotected compound 5 (70 g, 89.7%) as a yellow solid. Mp 106-108° C.

[0356] 1H NMR (DMSO-d6, 200 MHz): δ 7.88-7.73 (m, 2H), 5.33-4.76 (m,5H), 4.43 (s, 2H), 3.92-3.55 (m, 2H), 1.82-1.58 (m, 6H); Mass (CImethod): 358, 274, 244; IR (KBr, cm−1): 1719, 1520, 1338.

Preparation 26

[0357] General procedure for the conversion of

[0358] where ‘Ox’ represents a five membered heterocyclic group,containing at least one nitrogen atom and one more heteroatom selectedfrom oxygen, nitrogen or sulfur. In which, the said atleast one nitrogenatom connecting said heterocyclic moiety ‘Ox’ to the ‘Ar’ moiety. Theheterocyclic moiety is substituted by an ═O or ═S. The heterocycle mayalso be substituted by one or two additional substituents which are asdefined on the heterocyclic moiety of formula (I). The heterocycle mayalso be fused with substituted or unsubstituted phenyl group. ‘Ar’represents substituted or unsubstituted phenyl ring, the substituentsare as defined on the phenyl ring of the formula (I).

[0359] A solution of the nitro compound in THF was hydrogenated over 10%Pd on charcoal (catalytic amount) overnight. After the completeconsumption of starting material, a 5% solution of Na₂CO₃ (2.2 eq) inwater was added followed benzyl chloroformate (1.2 eq) at 0° C. Afterstirring the reaction mixture for 3 h at room temperature, it wasfiltered over celite bed and washed with ethyl acetate. The organiclayer was separated from the filtrate and washed with water twicefollowed by brine. The organic extract was dried, evaporated andpurified on a column of silica gel.

Reference Example of the Above Procedure Preparation 26A{3,5-Difluoro-4-[4-oxo-3-(tetrahydro-pyran-2-yloxymethyl)-imidazolidin-1-yl]-phenyl}-carbamicAcid Benzyl Ester

[0360]

[0361] A solution of Na₂CO₃ (10 g) in water (100 mL) was added to asolution of nitro (65 g, 182 mmol), obtained in preparation 25, in THF(400 mL) and the reaction mixture was hydrogenated over 10% Pd oncharcoal (20 g) overnight. The resultant mixture was filtered on a padof celite and the filtrate was concentrated. The residue obtained uponevaporation of solvent was taken up in acetone (400 mL) and to that wasadded a solution of Na₂CO₃ (77.7 g, 720 mmol) in water (400 mL). Thereaction mixture was cooled in an ice bath at this stage and benzylchloroformate (50% in toluene, 73 mL, 216 mmol) was added dropwise over30 min. After stirring for a further 30 min, ice pieces were added tothe reaction mixture. The solid obtained was filtered and driedazeotropically with toluene (2×300 mL) to give the title compound (66 g,78.3%) as a tan colored solid. Mp 116-118° C.

[0362] 1H NMR (DMSO-d6, 200 MHz): δ 10.07 (s, 1H), 7.40-7.13 (m, 7H),5.15-4.70 (m, 7H), 3.89 (s, 2H), 3.79-3.34 (m, 2H), 1.67-1.46 (m, 6H);Mass (CI method): 461, 378, 270; IR (KBr, cm−1): 1696, 1517, 1239.

Preparation 27

[0363]

[0364] Sodium hydride (0.312 g, 7.8 mmol) and allyl bromide (0.73 mL,8.5 mmol) were added sequentially to a solution of starting material (3g, 6.5 mmol) in dry DMF (25 mL) at 0° C. under argon. The reactionmixture was stirred for 12 h at rt and then diluted with ethyl acetate.The organic layer was washed with water, brine and dried. The residueobtained upon evaporation of solvent was chromatographed over silica gelto afford the product (3.1 g, 95%).

[0365] 1H NMR (DMSO-d6, 500 MHz) δ 7.38-7.30 (m, 5H), 7.11 (d, J=11.6Hz, 2H), 5.86-5.79 (m, 1H), 5.14-5.10 (m, 4H), 5.01-4.93 (m, 3H),4.74-4.70 (m, 2H), 4.27 (d, J=5.2 Hz, 2H), 4.08-4.01 (m, 2H), 3.78-3.75(m, 1H), 3.47-3.44 (m, 1H), 1.71-1.40 (m, 6H). Mass (CI method): 502,418, 400. IR (KBr, cm−1): 1717, 1516, 1023.

Preparation 28

[0366]

[0367] N-Methylmorpholine N-oxide (0.135 g, 0.99 mmol) and osmiumtetroxide (0.25 wt. % in 2-methylpropan-2-ol, 0.65 mL, 0.05 mmol), wereadded sequentially to a solution of starting material (0.5 g, 0.99 mmol)obtained by preparation 27 in 10:1 acetone:water mixture (50 mL) at20-35° C. The reaction mixture was stirred for 48 h at 20-35° C. Theresidue obtained upon evaporation of volatiles was chromatographed oversilica gel to afford the product (0.454 g, 80%).

[0368] 1H NMR (DMSO-d6, 400 MHz) δ 7.38-7.30 (m, 5H), 7.18 (d, J=12.2Hz, 2H), 5.11 (s, 2H), 5.02-4.52 (m, 8H), 4.04 (s, 2H), 3.79-3.44 (m,5H), 1.80-1.40 (m, 6H). Mass (CI method): 427, 344, 326. IR (Neat,cm−1): 3436, 1708, 1516.

EXAMPLES

[0369] A. General procedure for the conversion of

[0370] where ‘Ox’ represents a five membered heterocyclic group,containing at least one nitrogen atom and one more heteroatom selectedfrom oxygen, nitrogen or sulfur. In which, the said atleast one nitrogenatom connecting said heterocyclic moiety ‘Ox’ to the ‘Ar’ moiety. Theheterocyclic moiety is substituted by an ═O or ═S. The heterocycle mayalso be substituted by one or two additional substituents which are asdefined on the heterocyclic moiety of formula (I). The heterocycle mayalso be fused with substituted or unsubstituted phenyl group. ‘Ar’represents substituted or unsubstituted phenyl ring, the substituentsare as defined on the phenyl ring of the formula (I).

[0371] To a solution of the starting material in dry THF at −78° C.under argon was added 1.6 M BuLi (1.2 eq) drop wise. The reactionmixture was stirred for 45 min at the same temperature and thenR(−)-glycidyl butyrate or S(+)-glycidyl butyrate (1.2 eq ) was added.Stirred for 1 h at −78° C. Then the cold bath was removed whilemonitoring with TLC. After 3-12 h, the reaction mixture was quenchedwith saturated NH4Cl solution and extracted with ethyl acetate. Thecombined organic extracts were washed with water, brine and dried. Theresidue obtained upon evaporation of solvents was chromatographed oversilica gel to afford the product.

Reference Example of the Above Procedure Example 1(S)-3-{3,5-Difluoro-4-[4-oxo-3-(tetrahydro-pyran-2-yloxymethyl)-imidazolidin-1-yl]-phenyl}-5-hydroxymethyl-oxazolidin-2-one

[0372]

[0373] To a solution of{3,5-difluoro-4-[4-oxo-3-(tetrahydro-pyran-2-yloxymethyl)-imidazolidin-1-yl]-phenyl}-carbamicacid benzyl ester (40 g, 86.8 mmol), obtained in preparation 26A, in dryTHF (600 mL) at −78° C. under argon atmosphere was added butyl lithium(1.6 M in hexanes, 70 mL, 104.2 mmol) dropwise over a period of 5 min.The reaction mixture was stirred at −78° C. for 1 h followed by additionof (R) (−)-glycidylbutyrate (14.7 mL, 104.2 mmol). The reaction mixturewas stirred initially at −78° C. for 1 h and then at room temperaturefor overnight. The reaction mixture was quenched by addition ofsaturated NH₄Cl solution and then extracted with ethyl acetate. Thecombined organic extracts were washed with water, brine and dried. Theresidue obtained upon evaporation of solvent was chromatographed oversilica gel and eluted with ethyl acetate to give the title compound as acream colored gummy solid (24 g, 63.5% yield).

[0374] 1H NMR (CDCl3, 400 MHz): δ 7.19-7.10 (m, 2H), 5.19-4.71 (m, 6H),4.17-3.53 (m, 8H), 1.80-1.46 (m, 6H); Mass (CI method): 427, 344; IR(neat, cm−1): 3421, 1721, 1518, 1023.

Example 2(R)-3-{3,5-Difluoro-4-[4-oxo-3-(tetrahydro-pyran-2-yloxymethyl)-imidazolidin-1-yl]-phenyl}-5-hydroxymethyl-oxazolidin-2-one

[0375]

[0376] To a solution of{3,5-difluoro-4-[4-oxo-3-(tetrahydro-pyran-2-yloxymethyl)-imidazolidin-1-yl]-phenyl}-carbamicacid benzyl ester (40 g, 86.8 mmol), obtained in preparation 26A, in dryTHF (600 mL) at −78° C. under argon atmosphere was added butyl lithium(1.6 M in hexanes, 70 mL, 104.2 mmol) dropwise over a period of 5 min.The reaction mixture was stirred at −78° C. for 1 h followed by additionof (S)(+)-glycidylbutyrate (14.7 mL, 104.2 mmol). The reaction mixturewas stirred initially at −78° C. for 1 h and then at room temperaturefor overnight. The reaction mixture was quenched by addition ofsaturated NH₄Cl solution and then extracted with ethyl acetate. Thecombined organic extracts were washed with water, brine and dried. Theresidue obtained upon evaporation of solvent was chromatographed oversilica gel and eluted with ethyl acetate to give the title compound as acream colored gummy solid (24 g, 63.5% yield).

[0377] 1H NMR (CDCl3, 400 MHz): δ 7.19-7.10 (m, 2H), 5.19-4.71 (m, 6H),4.17-3.53 (m, 8H), 1.80-1.46 (m, 6H); Mass (CI method): 427, 344; IR(neat, cm−1): 3421, 1721, 1518, 1023.

Example 3(RS)-3-{3,5-Difluoro-4-[4-oxo-3-(tetrahydro-pyran-2-yloxymethyl)-imidazolidin-1-yl]-phenyl}-5-hydroxymethyl-oxazolidin-2-one

[0378]

[0379] A mixture of potassium carbonate (0.2 g, 1.5 mmol) and startingmaterial (0.5 g, 0.93 mmol), obtained in preparation 28, in DMF (5 mL)was heated to 60° C. for 30 min. The reaction mixture was allowed tocool to 25 to 35° C. and then worked up by adding aq. NH₄Cl followed byextraction with ethyl acetate. The organic layer was washed with water,brine and dried. The residue obtained upon evaporation of solvent wasdirectly used in the next step (0.367 g, 92%).

[0380] 1H NMR (CDCl₃, 400 MHz): δ 7.19-7.10 (m, 2H), 5.19-4.71 (m, 6H),4.17-3.53 (m, 8H), 1.80-1.46 (m, 6H); Mass (CI method): 427, 344; IR(neat, cm−¹): 3421, 1721, 1518, 1023.

[0381] Similarly Examples 4-22, 23-24 and 25-26 have been prepared by aperson skilled in the art according to the methodology as described inExamples 1, 2 and 3 respectively. Example No. Structure Analytical Data4

1HNMR (DMSO-d6, 200MHz): δ 7.68-7.50(m, 2H), 7.38(d, J=8.8Hz, 1H),5.23(t, J=5.8Hz, 1H), 4.73-4.72(m, 1H), 4.47(t, J=7.4Hz, 2H),4.14-3.80(m, 4H), 3.68-3.56(m, 2H). 5

1HNMR (CDCl3, 200MHz): δ7.73(d, J=11.6Hz, 1H), 7.52(t, J=8.8Hz, 1H),7.29(d, J=8.8Hz, 1H), 4.89(bs, 1H), 4.76(t, J=2H), 4.17(t, J=8.8Hz, 2H),3.93-3.68(m, 4H). 6

1HNMR (CDCl3, 200MHz): δ7.70(dd, J=12.7Hz and 2.2Hz, 1H), 7.44-7.26(m,2H), 4.75-4.68(m, 2H) 4.37(t, J=7.8Hz, 2H), 4.04-3.56(m, 4H), 3.48(t,J=7.8Hz, 2H). 7

1HNMR (CDCl3, 200MHz): δ7.62(dd, J=2.4Hz and 12.7Hz, 1H), 7.47(t,J=8.4Hz, 1H), 7.24-7.20(m, 1H), 4.77-4.69(m, 1H), 4.10-3.81(m, 5H),3.77-3.68(m, 4H), 3.23(s, 3H). 8

1HNMR (CDCl3, 200MHz): δ7.85-7.79(m, 1H), 7.58(t, J=8.0Hz, 1H),7.46-7.42(m, 1H), 7.30-7.18(m, 4H), 6.90-6.87(m, 1H), 4.90-4.75(m, 1H),4.15-4.07(m, 3H), 3.87-3.81(m, 1H). 9

1HNMR (CDCl3, 200MHz): δ7.76(dd, J=2.4Hz and 12.2Hz, 1H), 7.53-7.26(m,2H), 7.11(s, 1H), 6.97(d, J=8.4Hz, 1H), 6.72(d, J=7.8Hz, 1H),4.81-4.65(m, 1H), 4.09-3.82(m, 4H), 2.41(s, 3H), 2.09(hump, 1H). 10

1HNMR (CDCl3, 200MHz): δ7.77(d, J=10.4Hz, 1H), 7.57-7.26(m, 3H), 6.96(d,J=7.8Hz, 1H), 6.64(s, 1H), 4.82-4.71(m, 1H), 4.14-4.05(m, 3H),3.84-3.78(m, 2H), 2.35(s, 3H). 11

1HNMR (CDCl3, 200MHz): δ7.92-7.89(m, 2H), 7.44(d, J=7.8Hz, 1H),7.80-7.71(m, 1H), 4.54(t, J=7.2Hz, 2H), 4.08-3.89(m, 6H), 2.16(s, 1H).12

1HNMR (CDCl3, 200MHz): δ7.69-7.48(m, 2H), 7.23(d, J=8.8Hz, 1H),4.81-4.72(m, 1H), 4.54(t, J=7.4Hz, 2H), 4.13-3.69(m, 6H). 13

1HNMR (CDCl3, 200MHz): δ7.29(d, J=10.8Hz, 2H), 4.80-4.73(m, 1H), 4.57(t,J=15.6Hz, 2H), 4.00-3.73(m, 8H). 14

1HNMR (CDCl3, 200MHz): δ7.59(s, 4H), 5.24(t, J=5.4Hz, 1H), 4.67(bs, 1H),4.45(t, J=7.4Hz, 2H), 4.13-4.02(m, 3H), 3.88-3.54(m, 3H). 15

1HNMR (CDCl3, 200MHz): δ7.79(d, J=9.2Hz, 2H), 7.72(d, J=9.2Hz, 2H),7.59-7.03(m, 4H), 5.18(t, J=5.8Hz, 1H), 4.80-4.71(m, 1H), 4.18-4.02(m,2H), 3.98-3.68(m, 2H). 16

1HNMR (CDCl3, 200MHz): δ2.9(s, 3H), 4.1(t, 1H), 3.9(m, 6H), 4.7(m, 1H),4.8(s, 2H), 6.8(t, 1H), 7.2(d, 1H). 17

1HNMR (CDCl3, 200MHz): δ7.4(dd, J=2Hz and 15.4Hz, 1H), 7.2(d, J=8.8Hz,2H), 7.0(d, J=9.4Hz, 1H), 6.85(d, J=8.4Hz, 2H), 6.5(t, J=9.2Hz, 1H),4.75(s, 3H), 4.50(s, 2H), 3.95(m, 6H), 3.8(s, 3H). 18

1HNMR (CDCl3, 200MHz): δ7.55(dd, J=2.4Hz and 13.4Hz, 1H), 7.45(t,J=8.8Hz, 1H), 7.10(dd, J=2.2Hz and 13.0Hz, 1H), 4.66(m, 1H), 3.81(m,6H), 3.47(t, 2H), 2.8(s, 3H). 19

1HNMR (CDCl3, 200MHz): δ2.8(s, 3H), 3.4(m, 3H), 4.7(m, 1H), 7.5(m, 4H).20

1HNMR (CDCl3, 200MHz): δ7.7-7.2(m, 9H), 4.8-4.6(m, 1H), 4.5(s, 2H),4.1-3.7(m, 6H). 3.4(t, J=8.8Hz, 2H) 21

1HNMR (CDCl3, 200MHz): δ7.5-7.7(m, 4H), 7.3-7.4(m, 2H), 7.2(d, J=8.8Hz,1H), 7.1(t, 4H), 4.7(m, 1H), 3.9-4.1(m, 6H), 3.9(s, 1H), 3.7(m, 1H). 22

1HNMR (CDCl3, 200MHz): δ7.5(m, 4H), 7.2(m, 1H), 7.0(m, 2H), 4.7(m, 2H),4.0(m, 7H), 3.8(m, 1H). 23

1HNMR (CDCl3, 200MHz): δ2.9(s, 3H), 4.1(t, 1H), 3.9(m, 6H), 4.7(m, 1H),4.8(s, 2H), 6.8(t, 1H), 7.2(d, 1H). 24

1HNMR (CDCl3, 200MHz): δ7.4(dd, J=2Hz and 15.4Hz, 1H), 7.2(d, J=8.8Hz,2H), 7.0(d, J=9.4Hz, 1H), 6.85(d, J=8.4Hz, 2H), 6.5(t, J=9.2Hz, 1H),4.75(s, 3H), 4.50(s, 2H), 3.95(m, 6H), 3.8(s, 3H). 25

1HNMR (CDCl3, 200MHz): δ2.9(s, 3H), 4.1(t, 1H), 3.9(m, 6H), 4.7(m, 1H),4.8(s, 2H), 6.8(t, 1H), 7.2(d, 1H). 26

1HNMR (CDCl3, 200MHz): δ7.4(dd, J=2Hz and 15.4Hz, 1H), 7.2(d, J=8.8Hz,2H), 7.0(d, J=9.4Hz, 1H), 6.85(d, J=8.4Hz, 2H), 6.5(t, J=9.2Hz, 1H),4.75(s, 3H), 4.50(s, 2H), 3.95(m, 6H), 3.8(s, 3H).

[0382] B. General procedure for the conversion of

[0383] where ‘Ox’ represents a five membered heterocyclic group,containing at least one nitrogen atom and one more heteroatom selectedfrom oxygen, nitrogen or sulfur. In which, the said atleast one nitrogenatom connecting said heterocyclic moiety ‘Ox’ to the ‘Ar’ moiety. Theheterocyclic moiety is substituted by an ═O or ═S. The heterocycle mayalso be substituted by one or two additional substituents which are asdefined on the heterocyclic moiety of formula (I). The heterocycle mayalso be fused with substituted or unsubstituted phenyl group. ‘Ar’represents substituted or unsubstituted phenyl ring, the substituentsare as defined on the phenyl ring of the formula (I)

[0384] To a solution of the alcohol, triethylamine (2.2 eq) in drydichloromethane, methane sulfonylchloride (1.1 eq) was added at 0° C.under argon. The reaction mixture was warmed to room temperature over 2h and then diluted with dichloromethane. The organic layer was washedwith water, brine and dried. The residue obtained upon evaporation ofthe solvent was taken up in dry DMF and then NaN3 (1.5 eq) was added atroom temperature. The resultant mixture was heated to 80° C. for 2-5 hwhile monitoring by TLC. Allowed the reaction mixture to attain roomtemperature, water was added and extracted with ethyl acetate. Thecombined organic extracts were washed with water (3 times), brine anddried. The residue obtained upon evaporation of the solvent was passedthrough column to obtain the azide.

Reference Example of the Above Procedure Example 27(S)-5-Azidomethyl-3-{3,5-difluoro-4-[4-oxo-3-(tetrahydro-pyran-2-yloxymethyl)-imidazolidin-1-yl]-phenyl}-oxazolidin-2-one

[0385]

[0386] To a solution of(S)-3-{3,5-difluoro-4-[4-oxo-3-(tetrahydro-pyran-2-yloxymethyl)-imidazolidin-1-yl]-phenyl}-5-hydroxymethyl-oxazolidin-2-one(31 g, 72.6 mmol), obtained in Example 1, in dry dichloromethane (500mL) at 0° C. under argon atmosphere was added triethylamine (30 mL, 223mmol) followed by methanesulfonylchloride (7 mL, 89.9 mmol) drop wiseover a period of 10 min. The reaction mixture was stirred at 0° C. for 1h and was worked up by adding water followed by extracting withdichloromethane. The combined organic extracts were washed with water,brine and dried. The solvent was evaporated to give the correspondingmesylate as a gum, which was taken up for the next step without anypurification.

[0387] To a solution of the above crude mesylate in dry DMF (400 mL)under argon atmosphere was added sodium azide (6.76 g, 103.9 mmol) andthe resulting mixture was stirred at 80° C. for 2 h. The reactionmixture was allowed to cool to room temperature and worked up by addingwater followed by extraction with ethyl acetate. The combined organicextracts were washed with water, brine and dried. The residue obtainedupon evaporation of solvent was the title compound (29 g, 92.6% crudeyield for two steps) and was directly used for the next step withoutfurther purification.

[0388] 1H NMR (CDCl3, 400 MHz): δ 7.20-7.10 (m, 2H), 5.20-4.75 (m, 6H),4.15-3.45 (m, 8H), 1.85-1.45 (m, 6H); Mass (CI method): 452, 369, 244;IR (neat, cm−1): 2109, 1756, 1721, 1518.

[0389] Similarly Examples 28-41 have been prepared by a person skilledin the art according to the methodology as described in the aboveExample 27. Example No. Structure Analytical Data 28

1H NMR (CDCl3, 400MHz): δ7.20-7.10(m, 2H), 5.20-4.75(m, 6H),4.15-3.45(m, 8H), 1.85-1.45(m, 6H); Mass (CI method): 452, 369, 244; IR(neat, cm-1): 2109, 1756, 1721, 1518. 29

1H NMR (CDCl3, 400MHz): δ7.20-7.10(m, 2H), 5.20-4.75(m, 6H),4.15-3.45(m, 8H), 1.85-1.45(m, 6H); Mass (CI method): 452, 369, 244; IR(neat, cm-1): 2109, 1756, 1721, 1518. 30

1HNMR (DMSO-d6, 200MHz): δ 7.67-7.52(m, 2H), 7.38(d, J=8.8Hz, 1H),4.95-4.88(m, 1H), 4.47(t, J=7.2Hz, 2H), 4.16(t, J=9.4Hz, 1H),4.02-3.64(m, 5H). 31

1HNMR (CDCl3, 200MHz): δ7.62(dd, J=2.4Hz and 12.7Hz, 1H), 7.48(t,J=8.4Hz, 1H), 7.22-7.17(m, 1H), 4.85-4.73(m, 1H), 4.16-3.52(m, 8H),3.22(s, 3H). 32

1HNMR (CDCl3, 200MHz): δ7.75(dd. J=2.0Hz and 12.2Hz, 1H), 7.54(t,J=8.8Hz, 1H), 7.40-7.26(m, 1H), 7.10(s, 1H), 6.97(d, J=7.8Hz, 1H),6.71(d, J=6.8Hz, 1H), 4.87-4.79(m, 1H), 4.17-3.57(m, 4H), 2.41(s, 3H).33

1HNMR (CDCl3, 200MHz): δ7.81(d, 1H), 7.54(t, 1H), 7.45-7.01(m, 3H),6.67(s, 1H), 4.91-4.79(m, 1H), 3.95-3.47(m, 4H), 2.38(s, 3H). 34

1HNMR (CDCl3, 200MHz): δ7.89(d, J=7.4Hz, 2H), 7.43(d, J=9.4Hz, 1H),4.87-4.80(m, 1H), 4.54(t, J=7.2Hz, 2H), 4.12(t, J=8.8Hz, 2H),3.97-3.55(m, 4H). 35

1HNMR (CDCl3, 200MHz): δ7.71-7.50(m, 2H), 7.17(d, J=8.8Hz, 1H),4.89-4.75(m, 1H), 4.52(t, J=7.2Hz, 2H), 4.47-3.55(m, 6H). 36

1HNMR (CDCl3, 200MHz): δ7.31(s, 2H), 4.83-4.81(m, 1H), 4.57(t, J=7.8Hz,2H), 4.09-3.55(m, 6H). 37

1HNMR (DMSO-d6, 200MHz): δ 7.64(s, 4H), 4.98-4.89(m, 1H), 4.50(t,J=7.4Hz, 2H), 4.25-4.07(m, 4H), 3.88-3.70(m, 2H). 38

1HNMR (CDCl3, 200MHz): δ7.75(d, J=9.2Hz, 2H), 7.59(d, J=9.2Hz, 2H)7.48-7.03(m, 4H), 4.89-4.81(m, 1H), 4.16(t, J=9.2Hz, 1H), 3.98-3.58(m,3H). 38

¹HNMR (CDCl₃, 200MHz): δ7.75(d, J=9.2Hz, 2H), 7.59(d, J=9.2Hz, 2H)7.48-7.03(m, 4H), 4.89-4.81(m, 1H), 4.16(t, J=9.2Hz, 1H), 3.98-3.58(m,3H). 39

¹HNMR (CDCl₃, 200MHz): δ7.5-7.4(dd, 1H), 7.1(dd, 1H), 6.5(t, 1H), 4.9(s,2H), 4.8-4.7(m, 1H), 4.1-3.5(m, 6H), 3.0(s, 3H). 40

¹HNMR (CDCl₃, 200MHz): δ7.6(m, 4H), 7.35(t, 2H), 7.0-7.2(m, 2H), 4.8(m,1H), 4.1(m, 1H), 4.0(s, 4H), 3.9(m, 1H), 3.7(m, 2H). 41

¹HNMR (CDCl₃, 200MHz): δ7.6(m, 4H), 7.2(m, 1H), 7.0(m, 2H), 4.8(m, 1H),4.1(m, 1H), 4.0(s, 4H), 3.9(m, 1H), 3.6(m, 2H).

Example 42(S)-5-Azidomethyl-3-[3,5-difluoro-4-(3-hydroxymethyl-4-oxo-imidazolidin-1-yl)-phenyl]-oxazolidin-2-one

[0390]

[0391] A solution of5-azidomethyl-3-{3,5-difluoro-4-[4-oxo-3-(tetrahydro-pyran-2-yloxymethyl)-imidazolidin-1-yl]-phenyl}-oxazolidin-2-one(29 g, 64.1 mmol), obtained in example 27, and pyridinium p-toluenesulfonate (1.61 g, 6.4 mmol) in ethanol (300 mL) was refluxed for 4 h.The white solid obtained upon cooling the reaction mixture was filteredand washed with ethanol to afford the title compound (20 g, 86%). Mp.148-150° C.

[0392]¹H NMR (DMSO-d₆, 200 MHz): δ 7.34 (d, J=12.2 Hz, 2H), 6.10 (t,J=6.8 Hz, 1H), 5.00-4.80 (m, 3H), 4.72 (d, J=7.3 Hz, 2H), 3.96 (s, 2H),4.20-3.60 (m, 4H; Mass (CI method): 339, 311, 214; IR (KBr, cm⁻¹): 3374,2108, 1737, 1690.

[0393] Similarly Examples 43 and 44 have been prepared by a personskilled in the art according to the methodology as described in theExample 42 Example No. Structure Analytical Data 43

¹H NMR (DMSO-d₆, 200MHz): δ 7.34(d, J=12.2Hz, 2H), 6.10(t, J=6.8Hz, 1H),5.00-4.80(m, 3H), 4.72(d, J=7.3Hz, 2H), 3.96(s, 2H), 4.20-3.60(m, 4H);Mass (CI method): 339, 311, 214; IR (KBr, cm⁻¹): 3374, 2108, 1737, 169044

¹H NMR (DMSO-d₆, 200MHz): δ 7.34(d, J=12.2Hz, 2H), 6.10(t, J=6.8Hz, 1H),5.00-4.80(m, 3H), 4.72(d, J=7.3Hz, 2H), 3.96(s, 2H), 4.20-3.60(m, 4H);Mass (CI method): 339, 311, 214; IR (KBr, cm⁻¹): 3374, 2108, 1737, 1690

Example 45(S)-5-Azidomethyl-3-[3,5-difluoro-4-(4-oxo-imidazolidin-1-yl)-phenyl]-oxazolidin-2-one

[0394]

[0395] To a solution of5-azidomethyl-3-[3,5-difluoro-4-(3-hydroxymethyl-4-oxo-imidazolidin-1-yl)-phenyl]-oxazolidin-2-one(15 g, 40.7 mmol), obtained in example 42, in dry THF (200 mL) at 0° C.was added sodium hydride (60% in oil, 4.07 g, 101.9 mmol, washed twicewith dry hexane and dried at vacuum) in batches over 30 min. Thereaction mixture was allowed to warm to room temperature over 4 h andstirred for a further 16 h before being quenched with aq. NH₄Cl solutionat ice bath temperature. The reaction mixture was extracted with ethylacetate and the combined organic extracts were washed-with brine anddried. Evaporation of the solvent afforded the title compound (13 g, 94%for crude) as a colorless solid. Mp. 186-188° C.

[0396]¹H NMR (DMSO-d₆, 200 MHz): δ 8.59 (bs, 1H), 7.35 (d, J=12.2 Hz,2H), 5.00-4.80 (m, 1H), 4.75 (s, 2H), 3.85 (s, 2H), 4.20-4.62 (m, 4H);Mass (CI method): 339, 311, 214; IR (KBr, cm⁻¹): 2115, 1733, 1526.

[0397] Similarly examples 46 and 47 have been prepared by a personskilled in the art according to the methodology as described in theExample 45 Example No. Structure Analytical Data 46

¹H NMR (DMSO-d₆, 200MHz): δ8.59(bs, 1H), 7.35(d, J=12.2Hz, 2H),5.00-4.80(m, 1H), 4.75(s, 2H), 3.85(s, 2H), 4.20-4.62(m, 4H); Mass (CImethod): 339, 311, 214; IR (KBr, cm⁻¹): 2115, 1733, 1526. 47

¹H NMR (DMSO-d₆, 200MHz): δ8.59(bs, 1H), 7.35(d, J=12.2Hz, 2H),5.00-4.80(m, 1H), 4.75(s, 2H), 3.85(s, 2H), 4.20-4.62(m, 4H); Mass (CImethod): 339, 311, 214; IR (KBr, cm⁻¹): 2115, 1733, 1526.

Example C

[0398] General procedure for the conversion of

[0399] where Y² is as defined for formula (I); ‘Ar’ representssubstituted or unsubstituted phenyl ring, the substituents are asdefined on the phenyl ring of the formula (I).

[0400] Sodium hydride (1 eq.) was added to a solution of the startingazide (1 eq.) in dry DMF. The reaction mixture was stirred for 30 minand then quenched with appropriate alkyl halide. After stirring for afurther 2 h, the reactioin mixture was added to ice cold water andextracted with ethyl acetate. The organic layer was washed with water,brine and dried. The residue obtained upon evaporation of solvent waspassed through a column of silica gel to afford the respective alkylatedazide.

Reference Example of the Above Procedure Example 48(S)-Methoxythiocarbonylaminomethyl-2-oxo-oxazolidin-3-yl]-phenyl}-5-oxo-imidazolidin-1-yl)-aceticAcid Tert-butyl Ester

[0401]

[0402] Sodium hydride (0.17 g, 4.3 mmol)) was added to a solution of thestarting azide (1.2 g, 3.6 mmol), obtained in example 45, in dry DMF.The reaction mixture was stirred for 30 min and then quenched withappropriate alkyl halide. After stirring for a further 2 h, the reactionmixture was added to ice cold water and extracted with ethyl acetate.The organic layer was washed with water, brine and dried. The residueobtained upon evaporation of solvent was passed through a column ofsilica gel to afford the final compound (Yield: 1.5 g, 94%).

[0403]¹H NMR (DMSO-d₆, 200 MHz): δ 7.32 (d, J=11.7 Hz, 2H), 4.86-4.80(m, 1H), 4.78 (s, 2H), 4.12-3.60 (m, 8H), 1.40 (s, 9H).

[0404] Similarly Example 49 has been prepared by a person skilled in theart according to the methodology as described in the Example 48 ExampleNo. Structure Analytical Data 49

¹H NMR (CDCl₃, 200MHz): δ 7.48(dd, J=15.1 & 2.4Hz, 1H), 7.10(d, J=8.3Hz,1H), 6.70-6.50(m, 1H), 5.00-4.70(m, 3H), 4.10-3.30(m, 8H), 2.00-0.70(m,7H).

[0405] D. General procedure for the conversion of

[0406] where ‘Ox’ represents a five membered heterocyclic group,containing at least one nitrogen atom and one more heteroatom selectedfrom oxygen, nitrogen or sulfur. In which, the said at least onenitrogen atom connecting said heterocyclic moiety ‘Ox’ to the ‘Ar’moiety. The heterocyclic moiety is substituted by an ═O or ═S. Theheterocycle may also be substituted by one or two additionalsubstituents which are as defined on the heterocyclic moiety of formula(I). The heterocycle may also be fused with substituted or unsubstitutedphenyl group. ‘Ar’ represents substituted or unsubstituted phenyl ring,the substituents are as defined on the phenyl ring of the formula (I)

Procedure (i)

[0407] A solution of the azide in THF: MeOH (1:3) was hydrogenated over10% Pd on charcoal overnight. The reaction mixture was filtered and thefiltrate was concentrated. The residue was crystallized in MeOH toafford the amine.

Procedure (ii)

[0408] Triphenyl phosphine (1.3 eq) was added portion wise to a solutionof the azide in dry THF and the resultant mixture was stirred at roomtemperature for 6 h. Water (few drops) was added and the reactionmixture was heated to 60° C. overnight. The solvent was evaporated andthe residue was passed through a column of silica gel to afford theamine.

Reference Example of the Above Procedure Example 50(5S)-Aminomethyl-3-[3,5-difluoro-4-(4-oxo-imidazolidin-1-yl)-phenyl]-oxazolidin-2-one

[0409]

[0410] Triphenyl phosphine (33.5 g, 127.8 mL) was added portion wise toa solution of the azide (36 g, 106.5 mmol), obtained in example 45, indry THF and the resultant mixture was stirred at room temperature for 6h. Water (few drops) was added and the reaction mixture was heated to60° C. overnight. The solvent was evaporated and the residue was passedthrough a column of silica gel to afford the amine (31 g, 93%).

[0411]¹H NMR (200 MHz, DMSO-d₆) δ: 8.56 (s, 1H), 7.31 (d, J=12.8 Hz,2H), 4.70-4.62 (m, 3H), 4.02 (t, J=8.8 Hz, 1H), 3.97-3.80 (m, 3H), 3.33(s, 4H); MP: 192-194° C.

[0412] Similarly Examples 51-63 have been prepared by a person skilledin the art according to the methodology as described in the Example 50.Example No. Structure Analytical Data 51

¹H NMR (200MHz, DMSO-d₆) δ: 8.56(s, 1H), 7.31(d, J=12.8Hz, 2H),4.70-4.62(m, 3H), 4.02(t, J=8.8Hz, 1H), 3.97-3.80(m,3H), 3.33(s, 4H). 52

¹H NMR (200MHz, DMSO-d₆) δ: 8.56(s, 1H), 7.31(d, J=12.8Hz, 2H),4.70-4.62(m, 3H), 4.02(t, J=8.8Hz, 1H), 3.97-3.80(m, 3H), 3.33(s, 4H).53

¹HNMR (DMSO-D⁶, 200MHz): δ 7.66-7.50(m, 2H), 7.37(D, j=9.4Hz, 1H),4.66-4.60(m, 1H), 4.47(t, J=7.8Hz, 2H), 4.12-3.83(m, 6H), 2.91-2.80(m,2H). 54

¹HNMR (CDCl₃, 200MHz): δ7.63-7.55(dd, J=2.0Hz and 13.0Hz, 1H),7.49-7.22(m, 2H), 4.63-4.60(m, 1H) 4.09(t, J=8.8Hz, 1H), 4.03-3.73(m,4H), 3.32(m, 3H), 3.08(s, 3H). 55

¹HNMR (CDCl₃, 200MHz): δ8.02(s, 2H), 7.87-7.83(m, 2H), 7.64(s, 1H),7.50(d, J=8.2Hz, 1H), 4.84(s, 1H), 4.54(t, J=7.4Hz, 2H), 4.20-3.90(m,6H). 56

¹HNMR (DMSO-d⁶, 200MHz): δ 7.57(s, 4H), 4.63-4.61(m, 1H), 4.44(t,J=7.2Hz, 2H), 4.08-3.82(m, 4H), 2.86-2.82(m, 2H). 57

¹HNMR (CDCl₃, 200MHz): δ7.6-7.4(dd, 1H), 7.1(dd, 1H), 6.6(t, 1H), 4.9(s,2H), 4.6(m, 1H), 4.1-3.7(m, 4H), 3.2-2.8(m, 4H). 58

¹HNMR (CDCl₃, 200MHz): δ7.62-7.40(m, 3H), 7.3(s, 5H), 4.7(m, 1H), 4.5(s,2H), 4.1(t, 1H), 3.9-3.8(m, 4H), 3.4(t, 2H). 59

¹H NMR (200MHz, DMSO-d₆) δ: 7.55(s, 4H), 4.58-4.55(m, 1H), 4.41(t,J=7.8Hz, 2H), 4.02(t, J=7.0Hz, 2H), 3.83(t, J=6.8Hz, 2H), 3.44-2.78(m,4H). MP: 189-191° C. 60

¹H NMR (DMSO-d₆, 200MHz): δ 7.32(d, J=12.2Hz, 2H), 4.76(s, 2H),4.61-4.58(m, 1H), 4.05-3.10(m, 6H), 2.83(s, 3H). 61

¹H NMR (DMSO-d₆, 200MHz): δ 7.50(dd, J=15.8 & 2.2Hz, 1H), 7.20(d,J=8.6Hz, 1H), 6.92-6.80(m, 1H), 4.81(s, 2H), 4.60-4.50(m, 1H),4.10-3.70(m, 4H), 3.50-3.10(m, 2H), 2.90-2.70(m, 2H), 1.80-1.20(m, 4H),0.90(t, J=7.3Hz, 3H). 62

¹H NMR (DMSO-d₆, 200MHz): δ 7.32(d, J=12.2Hz, 2H), 4.76(s, 2H),4.61-4.58(m, 1H), 4.05-3.10(m, 6H), 2.83(s, 3H). 63

¹H NMR (DMSO-d₆, 200MHz): δ 7.32(d, J=12.2Hz, 2H), 4.76(s, 2H),4.61-4.58(m, 1H), 4.05-3.10(m, 6H), 2.83(s, 3H).

[0413] E. General procedure for the conversion of

[0414] where ‘Ox’ represents a five membered heterocyclic group,containing at least one nitrogen atom and one more heteroatom selectedfrom oxygen, nitrogen or sulfur. In which, the said atleast one nitrogenatom connecting said heterocyclic moiety ‘Ox’ to the ‘Ar’ moiety. Theheterocyclic moiety is substituted by an ═O or ═S. The heterocycle mayalso be substituted by one or two additional substituents which are asdefined on the heterocyclic moiety of formula (I). The heterocycle mayalso be fused with substituted or unsubstituted phenyl group. ‘Ar’represents substituted or unsubstituted phenyl ring, the substituentsare as defined on the phenyl ring of the formula (I)

[0415] A solution of amine in methyl formate was heated to 80° C.overnight. The volatiles were removed under low pressure and the residueobtained was passed through column to yield formate in very pure form.

[0416] Examples 64-66 have been prepared by a person skilled in the artaccording to the methodology as described in the above procedure E.Example No. Structure Analytical Data 64

¹HNMR (CDCl₃, 200MHz): δ8.28(s, 1H), 7.66-7.49(m, 2H), 7.15(d, J=8.8Hz,1H), 6.15(bs, 1H), 4.82(m, 1H), 4.52(t, J=7.4Hz, 2H), 4.48-4.02(m, 3H).65

¹HNMR (CDCl₃, 200MHz): δ8.27(s, 1H), 7.26-7.23(m, 2H), 6.32(bs, 1H),4.82(bs, 1H), 4.58(t, J=7.2Hz, 2H), 4.214-3.68(m, 6H).

[0417] F. General procedure for the conversion of

[0418] where ‘Ox’ represents a five membered heterocyclic group,containing at least one nitrogen atom and one more heteroatom selectedfrom oxygen, nitrogen or sulfur. In which, the said at least onenitrogen atom connecting said heterocyclic moiety ‘Ox’ to the ‘Ar’moiety. The heterocyclic moiety is substituted by an ═O or ═S Theheterocycle may also be substituted by one or two additionalsubstituents which are as defined on the heterocyclic moiety of formula(I). The heterocycle may also be fused with substituted or unsubstitutedphenyl group. ‘Ar’ represents substituted or unsubstituted phenyl ring,the substituents are as defined on the phenyl ring of the formula (I);and R^(4a) represents (C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, (C₂-C₁₀)alkenyl,halo(C₁-C₁₀)alkyl, aryloxy, (C₂-C₁₀)alkenyloxy, aryloxycarbonyl or(C₁-C₁₀)alkoxycarbonyl.

[0419] To a solution of the amine (1 eq) in dry dichloromethane at 0° C.under argon was added Et₃N (2.5 eq) followed by respective acid chloride(1.2 eq) drop wise. After being stirred at room temperature for 1 to 6 h(TLC control), the reaction mixture was diluted with dichloromethane andwashed with water twice followed by brine. The organic extract wasdried, evaporated and was passed through column to afford the acylatedproduct.

[0420] Representative examples of the above procedure

[0421] Examples 66-96 have been prepared by a person skilled in the artaccording to the methodology as described in the above procedure F.Example No. Structure Analytical Data 66

¹HNMR (CDCl₃, 200MHz): δ 7.62(dd, J=2.60Hz and 13.4Hz, 1H), 7.52(d,J=8.60Hz, 1H), 7.13-7.17(m, 1H), 5.96-5.99(m, 1H), 4.82-4.76(m, 1H),4.52(t, J=7.40Hz, 2H), 4.01-4.09(m, 3H), 3.62-3.81(m, 3H), 2.02(s, 3H).67

¹HNMR (CDCl₃, 200MHz): δ 7.66-7.49(m, 2H), 7.16(d, J=8.8Hz, 1H),6.03(bs, 1H), 4.82-4.78(m, 1H), 4.52(t, J=7.8Hz, 2H), 4.09-4.0(m, 3H),3.83-3.65(m, 3H), 2.24(q, J=7.8Hz, 2H), 1.13(t, J=7.8Hz, 3H). Mp: 203°C. 68

¹HNMR (CDCl₃, 200MHz): δ 7.66-7.49(m, 2H), 7.15(d, J=8.8Hz, 1H),6.01(bs, 1H), 4.81-4.75(m, 1H), 4.52(t, J=7.8Hz, 2H), 4.09-4.01(m, 3H),3.83-3.65(m, 3H), 2.19(t, J=7.4Hz, 2H), 1.65-1.58(m, 2H), 0.98(t,J=7.4Hz, 3H). Mp: 211° C. 69

¹HNMR (CDCl₃, 200MHz): δ 7.66-7.49(m, 2H), 7.15(d, J=8.8Hz, 1H),4.82-4.76(m, 1H), 4.52(t, J=7.8Hz, 2H), 4.09-4.01(m, 2H), 3.83-=3.65(m,3H), 2.21(t, J=7.4Hz, 2H), 1.57-1.49(m, 2H), 1.38-1.20(m, 2H), 0.89(t,3H). Mp: 187° C. 70

¹HNMR (CDCl₃, 200MHz): δ 7.68-7.52(m, 2H), 7.17(d, 8.6Hz, 1H),5.96(hump, 1H), 4.81(hump, 1H), 4.54(t, J=7.2Hz, 2H), 4.11-3.67(m, 6H),2.22(t, J=7.4Hz, 2H), 1.60(bs, 8H), 0.87(s, 3H). Mp: 131° C. 71

¹HNMR (CDCl₃ + DMSO-d⁶, 200MHz): δ 7.97(bs, 1H), 7.6-7.40(m, 2H),7.10(d, J=8.8Hz, 1H), 6.35-6.15(m, 2H), 5.63(dd, J=4.0Hz and 8.3Hz, 1H),4.79-4.86(m, 1H), 4.53(t, J=7.8Hz, 2H), 4.05(t, J=6.8Hz, 2H),3.89-3.56(m, 4H). Mp: 196° C. 72

¹HNMR (CDCl₃ + DMSO-d⁶, 200Mhz): δ 9.38(bs, 1H) 7.67-7.5(m, 2H), 7.20(d,J=8.8Hz, 1H), 4.88-4.87(m, 1H), 4.53(t, J=7.8Hz, 2H), 4.16-4.02(m, 3H),3.89-3.70(m, 1H), 3.67-3.65(m, 2H). Mp: 194° C. 73

¹HNMR (CDCl₃, 200MHz): δ 7.66-7.49(m, 2H), 7.15(d, J=8.8Hz, 1H),4.85-4.83(m, 1H), 5.55-4.47(m, 2H), 4.37-4.31(m, 2H), 4.14-3.90(m, 3H),3.88-3.60(m, 3H), 1.42(t, 3H). Mp: 160° C. 74

¹HNMR (CDCl₃, 200MHz): δ 7.75-7.05(m, 3H), 6.05(bs, 1H), 4.95-4.62(m2H), 4.52(t, 1H), 4.30-3.32(m, 6H), 2.023(s, 3H). 75

¹HNMR (CDCl₃, 200MHz): δ 7.5(d, J=7.81Hz, 2H), 7.3(d, J=7.81Hz, 2eH),4.8(s, 1H), 4.4(s, 4H), 4.1(t, 1H), 3.8(t, 1H), 3.5(s, 1H), 32.3(s, 1H),2.0(s, 3H). 76

¹HNMR (CDCl₃, 200MHz): δ 7.99(hump, 1H), 7./73(d, J=13.0Hz, 1H), 7.43(d,J=8.0Hz, 1H) 7.31(d, J=8.8Hz, 1H), 4.83(hump, 1H), 4.42(t, J=7.6Hz, 2H),4.15-3.89(m, 3H), 3.62-3.55(m, 4H), 2.0(s, 3H). Mp: 220° C. 77

¹HNMR (CDCl₃, 200MHz): δ 7.61(dd, J=2.6Hz and 12.7Hz, 1H), 7.48(t,J=8.4Hz, 1H), 7.19(dd, J=2.6Hz and 8.8Hz, 1H), 6.15(t, J=8.4Hz, 1H),4.79-4.77(m, 1H), 4.05(t, J=8.8Hz, 1H), 3.97-3.88(m, 2H), 3.81-3.74(m,3H), 3.69-3.61(m, 2H), 3.23(s, 3H), 2.03(s, 3H). Mp: 171° C. 78

¹HNMR (CDCl₃, 200MHz): δ 7.76(dd, J=2.2Hz and 12.0Hz, 1H), 7.53(t,J=8.4Hz, 1H), 7.37-7.14(m, 4H), 6.82(t, J=3.4Hz, 1H), 6.03(t, J=5.4Hz,1H), 4.83-4.80(m, 1H), 4.10(t, J=9.0Hz, 1H), 3.88-3.80(m, 1H),3.71-3.66(m, 2H), 2.04(s, 3H). 79

¹HNMR (CDCl₃, 200MHz): δ 7.74(dd, J=2.6Hz and 12.2Hz, 1H), 7.53(t,J=8.4Hz, 1H), 7.49-7.26(m, 2H), 7.10-6.95(m, 2H), 6.72-6.68(m, 1H),6.09-6.01(m, 1H), 4.84(bs, 1H), 4.10(t, J=8.8Hz, 1H), 3.88-3.66(m, 3H),2.41(s, 3H), 2.04(s, 3H). Mp: 213° C. 80

¹HNMR (CDCl₃, 200MHz): δ 7.80-6.94(m, 4H), 6.63(s, 1H), 6.0(bs, 1H),4.82-4.90(m, 1H), 4.11(t, J=9.2Hz, 1H), 3.89-3.66(m, 3H), 2.35(s, 3H),2.09(s, 3H). Mp: 202° C. 81

¹HNMR (CDCl₃, 200MHz): δ 7.93(s, 1H), 7.76(d, J=8.8Hz, 1H), 7.42(d,J=8.8Hz, 1H), 6.57(bs, 1H), 4.79(bs, 1H), 4.52(t, J=7.8Hz, 2H),4.11-3.60(m, 6H), 1.99(s, 3H). Mp: 143° C. 82

¹HNMR (CDCl₃, 200MHz): δ 7.93-7.79(m, 2H), 7.43(d, J=8.8Hz, 1H),6.12(bs, 1H), 4.82-4.78(m, 1H), 4.53(t, J=7.4Hz, 2H), 4.09(t, J=9.4Hz,1H), 3.96-3.66(m, 5H), 2.30-2.17(m, 2H), 1.20(t, J=9.4Hz, 3H). Mp: 143°C. 83

¹HNMR (CDCl₃, 200MHz): δ 7.91(s, 1H), 7.78(d, J=8.2Hz, 1H), 6.26(bs,1H), 4.80(bs, 1H), 4.52(t, J=7.2Hz, 2H), 4.06(t, J=9.4Hz, 1H),3.95-3.67(m, 5H), 2.47-2.05(m, 4H), 1.83-1.54(m, 6H), 0.83-0.78(m, 3H).Mp: hygroscopic 84

¹HNMR (CDCl₃, 200MHz): δ 7.92(s, 1H), 7.85(d, J=8.2Hz, 1H), 7.45(d,J=8.8Hz, 1H), 6.40-6.07(m, 3H), 5.75(d, J=10.4Hz, 1H), 4.89(hump, 1H),4.56(t, J=7.8Hz, 2H), 4.13(t, J=9.2Hz, 1H), 3.98-3.78(m, 5H). Mp: 191°C. 85

¹HNMR (CDCl₃, 200MHz): δ 7.65-7.41(m, 2H), 7.23(d, J=7.2Hz, 1H),6.12(bs, 1H), 4.80(bs, 1H), 4.52(t, J=7.8Hz, 2H), 4.47-4.00(m, 3H),3.81-3.59(m, 3H), 2.05(s, 3H). Mp: 120° C. 86

¹HNMR (CDCl₃, 200MHz): δ 7.27(d, J=9.8Hz, 2H), 6.01(hump, 1H),4.80(hump, 1H), 4.57(t, J=7.8Hz, 2H), 4.06-3.67(m, 6H), 2.03(s, 3H). Mp:219° C. 87

¹HNMR (CDCl₃ + DMSO-d⁶, 200MHz): δ 7.32-7.26(m, 2H), 7.09(hump, 1H),4.81(hump, 1H), 4.58(t, J=7.4Hz, 2H), 4.05-3.62(m, 6H), 2.25-2.18(m,2H), 1.11(t, J=7.8Hz, 3H). Mp: 224° C. 88

¹HNMR (CDCl₃ + DMSO-d6, 200MHz): δ 7.64(s, 2H), 7.55(s, 2H),7.09-7.25(m, 1H), 4.70-4.85(m, 1H), 4.46(t, 2H), 4.13-3.81(m, 4H),3.57(bs, 2H), 1.96(s, 3H). Mp: 231° C. 89

¹HNMR (CDCl₃, 200MHz): δ 7.70(d, J=8.8Hz, 2H), 7.54(d, J=8.8Hz, 2H),7.24-6.99(m, 4H), 6.19(bs, 1H), 4.80(m, 1H), 4.09(t, J=8.8Hz, 1H),3.85(t, J=7.0Hz, 1H), 3.69-3.63(m, 2H), 2.02(s, 3H). Mp: 229° C. 90

¹HNMR (CDCl₃, 200MHz): δ 7.10(d, 1H), 6.6(t, 1H), 6.0(m, 1H), 4.90(s,2H), 4.9(m, 1H), 4.0(s, 3H), 3.80(m, 3H), 3.0(s, 3H), 2.0(s, 3H). Mp:230° C. 91

¹HNMR (CDCl₃, 200MHz): δ 7.26-7.46(m, 6H), 7.01(d, 1H), 6.63(t, 1H),6.05(s, 1H), 4.71-4.89(m, 2H), 4.77(s, 1H), 4.60(s, 2H), 3.94-4.04(m,3H), 3.61-3.76(m, 3H), 2.01(s, 3H). 92

¹HNMR (CDCl₃, 200MHz): δ 7.50(m, 2H), 7.10(d, J=8.4Hz, 1H), 6.18(t, 1H),4.7(m, 1H), 4.0(t, J=9.4Hz, 1H), 3.6(m, 7H), 2.9(s, 3H), 2.0(s, 3H). Mp:182° C. 93

¹HNMR (CDCl₃, 200MHz): δ 2.0(s, 3H), 2.8(s, 3H), 4.0(t, 1H), 3.4-3.8(m,5H), 4.8(m, 1H), 6.2(m, 1H), 7.6(m, 4H). Mp: 217° C. 94

¹HNMR (CDCl₃, 200MHz): δ 7.6-7.3(m, 9H), 6.2(bt, 1H), 4.8-4.7(m, 1H),4.5(s, 2H), 4.06(t, J=9.3Hz, 1H), 3.90-3.3(m, 6H), 2.0(s, 3H). Mp: 204°C. 95

¹HNMR (CDCl₃, 200MHz): δ 7.70-7.50(m, 4H), 7.40-7.30(t, 2H), 7.2(d,J=8.8Hz, 1H), 7.1(t, 1H), 4.80(m, 5H), 4.0(m, 5H), 3.8(m, 1H), 3.6(m,2H), 2.0(s, 3H). Mp: 182° C. 96

¹HNMR (CDCl₃, 200MHz): δ 8.3(m, 1H), 7.6(m, 4H), 7.3(m, 1H), 7.2(t, 2H),4.7(m, 1H), 4.1(t, 1H), 3.8-4.0(m, 4H), 3.7(t, 1H), 3.0(m, 2H), 1.8(s,3H). Mp: 194° C.

[0422] G. General procedure for the conversion of

[0423] where ‘Ox’ represents a five membered heterocyclic group,containing at least one nitrogen atom and one more heteroatom selectedfrom oxygen, nitrogen or sulfur. In which, the said atleast one nitrogenatom connecting said heterocyclic moiety ‘Ox’ to the ‘Ar’ moiety. Theheterocyclic moiety is substituted by an ═O or ═S. The heterocycle mayalso be substituted by one or two additional substituents which are asdefined on the heterocyclic moiety of formula (I). The heterocycle mayalso be fused with substituted or unsubstituted phenyl group. ‘Ar’represents substituted or unsubstituted phenyl ring, the substituentsare as defined on the phenyl ring of the formula (I); and R^(4b)represents (C₁-C₁₀)alkyl, halo(C₁-C₁₀)alkyl, —C(═O)—(C₁-C₁₀)alkoxy,—C(═O)-aryloxy, —C(═S)—(C₁-C₁₀)alkyl or —C(═S)-aryl.

[0424] A solution of the amide (1 eq) and Lawesson's reagent (0.6 eq) indry dioxane was heated to 55 to 100° C. over 3 to 10 h (TLC control).The reaction mixture was allowed to cool to room temperature and dilutedwith ethyl acetate. The resultant mixture was washed with water (4times) followed by brine and dried. The residue obtained uponevaporation of solvent was passed through column of silica gel to affordthe respective thioacetate.

Reference Example of the Above Procedure Example 97(5S)-3-[3-Fluoro-4-(3-methyl-2-oxo-1-imidazolidinyl)phenyl]-5-(1-thioxoethylaminomethyl)-1,3-oxazolan-2-one

[0425]

[0426] A solution of the amide (100 mg, 0.28 mmol), obtained in example92, and Lawesson's reagent (69 mg, 0.17 mmol) in dry dioxane was heatedto 80 to 90° C. over 3 to 10 h (TLC control). The reaction mixture wasallowed to cool to room temperature and diluted with ethyl acetate. Theresultant mixture was washed with water (4 times) followed by brine anddried. The residue obtained upon evaporation of solvent was passedthrough column of silica gel to afford the final compound (Yield: 70 mg,67%).

[0427]¹HNMR (CDCl₃, 200 MHz): δ 8.4 (1H), 7.5 (m, 2H), 7.0 (d, J=8.8 Hz,2H), 4.9 (m, 1H), 3.9 (m, 6H), 3.5 (t, J=8.8 Hz, 2H), 2.9 (s, 3H), 2.5(s, 3H); Mp: 168° C.

[0428] Examples 98-108 have been prepared by a person skilled in the artaccording to the methodology as described in the above Example 97. Ex-am- ple No. Structure Analytical Data  98

¹HNMR(CDCl₃, 200MHz): δ7.94(bs, 1H), 7.66-7.52 (m, 2H), 7.16(d, J=7.8Hz,1H), 5.20-4.85(m, 1H), 4.54 (t, J=7.8Hz, 2H), 4.25-3.82 (m, 6H), 2.61(s,3H). Mp: 171° C.  99

¹HNMR(CDCl₃+DMSO-d6, 200MHz): δ10.51(s, 1H), 7.64-7.47(m, 2H), 7.16(d,J=8.8Hz, 1H), 5.01(bs, 1H), 4.53(t, J=7.2Hz, 2H), 4.29-3.89(m, 4H),3.63(q, J=10.2Hz, 2H). Mp: 165° C. 100

¹HNMR(CDCl₃, 200MHz): δ7.90(bs, 1H), 7.61(dd, J=2.4Hz and 12.8Hz, 1H),7.50(t, J=8.2Hz, 1H), 7.19 (dd, J=2.4Hz and 12.8Hz, 1H), 5.0(m, 1H),4.25-3.74 (m, 8H), 3.24(s, 3H), 2.6(s, 3H). Mp: 111°C. 101

¹HNMR(CDCl₃, 200MHz): δ7.87-7.74(m, 2H), 7.57(t, J=8.2Hz, 1H), 7.39-7.18(m, 4H), 6.87-6.85(m, 1H), 5.08-5.05(m, 1H), 4.37-4.27 (m, 1H),4.23-4.06(m, 2H), 3.94(t, J=6.8Hz, 1H), 2.62 (s, 3H). 102

¹HNMR(CDCl₃, 200MHz): δ8.1(s, 1H), 7.9(s, 1H), 7.8 (d, J=8.7Hz, 1H),7.4(d, J=8.79, 1H), 5.0(s, 1H), 4.6 (t, 2H), 4.0(m, 6H), 2.6(s, 3H). Mp:154° C. 103

¹HNMR(CDCl₃+DMSO-d⁶, 200MHz): δ10.37(bs, 1H), 7.50(d, J=10.8Hz, 2H),4.98(bs, 1H), 4.55(t, J=7.8 Hz, 2H), 4.23-3.78(m, 6H), 2.50(s, 3H). Mp:108° C. 104

¹HNMR(CDCl₃, 200MHz): δ7.86(bt, 1H), 7.28(d, J=9.6Hz, 2H), 5.02-4.99(m,1H), 4.58(t, J=7.4Hz, 2H), 4.24-3.80(m, 6H), 2.71(q, J=7.4Hz, 2H),1.29(t, J=7.8 Hz, 3H). Mp: 168° C. 105

¹HNMR(CDCl₃, 200MHz): δ7.86(hump, 1H), 7.25(d, J=9.6Hz, 2H),5.02-4.99(m, 1H), 4.58(t, J=7.4Hz, 2H), 4.24-3.80(m, 6H), 2.71(q,J=7.4Hz, 2H), 1.29(t, J=7.8 Hz, 3H). Mp: 195° C. 106

¹HNMR(CDCl₃, 200MHz): δ7.6(m, 4H), 7.4(m, 2H), 7.2(d, J=8.8Hz, 1H), 7.0(t, 1H), 5.0(m, 1H), 4.0(m, 8H), 2.6(s, 3H). Mp: 165°C. 107

¹HNMR(200MHz, DMSO- d₆) δ: 11.10(s, 1H), 10.40 (bs, 1H), 7.47(d,J=15.8Hz, 1H), 7.61(d, J=8.3Hz, 1H), 6.83(t, J=9.4Hz, 1H), 5.00(s, 2H),4.98-4.91 (m, 1H), 4.30(s, 2H), 4.20-3.65(m, 4H), 2.47(d, J=12.6Hz, 3H).108

¹HNMR(200Mz, DMSO- d₆) δ: 10.38(bs, 1H), 8.58(s, 1H), 7.31(d, J=12.2Hz,2H), 4.96(bs, 1H), 4.73(s, 2H), 4.14(t, J=9.0 Hz, 1H), 3.91-3.75(m, 5H),2.51(s, 3H). MP: 148-150° C.

[0429] H. General procedure for the conversion of

[0430] where ‘Ox’ represents a five membered heterocyclic group,containing at least one nitrogen atom and one more heteroatom selectedfrom oxygen, nitrogen or sulflur. In which, the said atleast onenitrogen atom connecting said heterocyclic moiety ‘Ox’ to the ‘Ar’moiety. The heterocyclic moiety is substituted by an ═O or ═S. Theheterocycle may also be substituted by one or two additionalsubstituents which are as defined on the heterocyclic moiety of formula(I). The heterocycle may also be fused with substituted or unsubstitutedphenyl group. ‘Ar’ represents substituted or unsubstituted phenyl ring,the substituents are as defined on the phenyl ring of the formula (I).

[0431] To a solution of the amine (1 eq), Et₃N (2.2 eq) in drydichloromethane and methyl chloroformate under argon was added at 0° C.(1.2 eq). The reaction mixture was stirred at room temperature overnightand worked up by diluting with dichloromethane followed by washing withwater and brine. The residue obtained after evaporation of the driedorganic layer was passed through column to afford the carbamate.

[0432] Examples 109-113 have been prepared by a person skilled in theart according to the methodology as described in the above procedure H.Example No. Structure Analytical Data 109

¹HNMR(CDCl₃, 200MHz): δ7.68-7.49(m, 2H), 7.16(d, J=8.4Hz, 1H), 5.16(bs,1H), 4.78(bs, 1H), 4.52(t, J=7.2 Hz, 2H), 4.09-4.0(m, 3H), 3.84-3.55(m,6H). Mp: 153° C. 110

¹HNMR(CDCl₃, 200MHz): δ7.9(m, 2H), 7.4(d, J=8.3Hz, 1H), 5.2(s, 1H),4.8(s, 1H), 4.5(t, 1H), 4.0(m, 9H). Mp: 148° C. 111

¹HNMR(CDCl₃, 200MHz): δ7.27(d, J=6.8Hz, 2H), 5.16 (bs, 1H), 4.84-4.80(m,1H), 4.58(t, J=7.2Hz, 2H), 4.07-3.60(m, 9H). Mp: 157° C. 112

¹HNMR(CDCl₃+DMSO-d⁶, 200MHz): δ7.57(s, 4H), 6.98 (bs, 1H), 4.96-4.76(m,1H), 4.51(t, J=7.4, 2H), .4.47 (m, 3H), 3.91-3.84(m, 1H), 3.65(s, 1H),3.51(bs, 3H). Mp: 195° C. 113

¹HNMR(CDCl₃, 200MHz): δ3.0(s, 3H), 3.8(m, 6H), 4.8 (m, 1H), 4.9(s, 2H),5.1(m, 1H), 6.6(t, 1H). Mp: 226° C.

[0433] I. General procedure for the conversion of

[0434] where ‘Ox’ represents a five membered heterocyclic group,containing at least one nitrogen atom and one more heteroatom selectedfrom oxygen, nitrogen or sulfur. In which, the said atleast one nitrogenatom connecting said heterocyclic moiety ‘Ox’ to the ‘Ar’ moiety. Theheterocyclic moiety is substituted by an ═O or ═S. The heterocycle mayalso be substituted by one or two additional substituents which are asdefined on the heterocyclic moiety of formula (I). The heterocycle mayalso be fused with substituted or unsubstituted phenyl group. ‘Ar’represents substituted or unsubstituted phenyl ring, the substituentsare as defined on the phenyl ring of the formula (I); and R^(4c)represents (C₁-C₁₀)alkyl group.

[0435] To an ice cold mixture of amine (1 eq), Et₃N (2 eq) and water(few drops) in EtOH CS₂ (1 eq) was added under argon. Stirred overnightat room temperature, Methyl iodide (MeI) (1.1 eq) in EtOH was added andthe stirring was continued for 12 h. The volatiles were removed and theresidue was taken up in ethyl acetate. The organic mixture was washedwith saturated NaHCO₃, water, brine and dried. The residue obtained waspassed through column to afford the product.

[0436] Examples 114 and 115 have been prepared by a person skilled inthe art according to the methodology as described in the above procedureI. Example No. Structure Analytical Data 114

¹HNMR(CDCl₃+ DMSO-d6, 200MHz): δ9.98(bt, 1H), 7.55 (s, 4H), 5.05-5.02(m,1H), 4.50(t, J=7.8Hz, 2H), 4.12-3.87(m, 6H), 2.60(s, 3H). Mp: 161° C.115

¹HNMR(DMSO-d6, 200MHz): δ7.26(s, 1H), 6.15 (d, J=10.2Hz, 2H), 4.56-4.49(m, 3H), 4.27-3.83(m, 5H), 3.26-3.15(m, 1H), 2.54(s, 3H). Mp: 147° C.

[0437] J. General procedure for the conversion of Step (i):

[0438] where ‘Ox’ represents a five membered heterocyclic group,containing at least one nitrogen atom and one more heteroatom selectedfrom oxygen, nitrogen or sulfur. In which, the said atleast one nitrogenatom connecting said heterocyclic moiety ‘Ox’ to the ‘Ar’ moiety. Theheterocyclic moiety is substituted by an ═O or ═S. The heterocycle mayalso be substituted by one or two additional substituents which are asdefined on the heterocyclic moiety of formula (I). The heterocycle mayalso be fused with substituted or unsubstituted phenyl group. ‘Ar’represents substituted or unsubstituted phenyl ring, the substituentsare as defined on the phenyl ring of the formula (I).

[0439] Thiophosgene (1.2 eq) was added drop wise to a solution of theamine (1 eq), Et₃N (2.4 eq) in dry dichloromethane at ice bathtemperature. The reaction may be carried out in the presence of argon.The reaction mixture was warmed to 20 to 35° C. over 3 h and then thevolatiles were removed. The residue obtained was directly charged on toa column of silica gel to afford the product.

Step (ii)

[0440]

[0441] where ‘Ox’ represents a five membered heterocyclic group,containing at least one nitrogen atom and one more heteroatom selectedfrom oxygen, nitrogen or sulfur. In which, the said atleast one nitrogenatom connecting said heterocyclic moiety ‘Ox’ to the ‘Ar’ moiety. Theheterocyclic moiety is substituted by an ═O or ═S. The heterocycle mayalso be substituted by one or two additional substituents which are asdefined on the heterocyclic moiety of formula (I). The heterocycle mayalso be fused with substituted or unsubstituted phenyl group. ‘Ar’represents substituted or unsubstituted phenyl ring, the substituentsare as defined on the phenyl ring of the formula (I); and R^(4d)represents (C₁-C₁₀)alkyl, cyclo(C₁-C₁₀)alkyl, -(C═O)—(C₁-C₁₀)alkyl groupsubstituted with fluorine; aryl such as phenyl or naphthyl;halo(C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl or(C₂-C₁₀)alkenyl.

[0442] A solution of the isothiocyanate in the respective alcohol washeated to 80 to 100° C. while monitoring by TLC. At the completeconsumption of starting material, the reaction mixture was allowed tocool to room temperature. The crystals formed were separated, washedwith ether and dried at vacuum to yield the pure product.

Reference Examples of the Above Procedure Example 116(S)-{3-[3,5-Difluoro-4-(4-oxo-imidazolidin-1-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-thiocarbamicAcid O-methyl Ester

[0443]

[0444] Step (i)

[0445] To a solution of the amine (13 g, 41.6 mmol), obtained in example50, in dichloromethane (100 mL) and DMF (100 mL) was added a solution ofNaHCO₃ (10.4 g, 124.8 mmol) in water (50 mL) followed by thiophosgene(3.8 mL, 49.9 mmol) at ice bath temperature. The reaction mixture wasstirred at 20-35° C. over 30 min and was worked up by adding waterfollowed by extraction of chloroform. The combined organic extracts werewashed with brine and the residue obtained upon evaporation of all thesolvents was washed with petroleum ether to afford the correspondingisothiocyanate (Yield: 12 g, 87%).

Step (ii)

[0446] A solution of the above obtained isothiocynate compound (24 g,67.7 mmol) in dry methanol (750 mL) was refluxed overnight. The residueobtained upon evaporation of methanol was purified on a column of silicagel to afford the title compound (Yield: 22 g, 84

[0447]¹H NMR (200 MHz, DMSO-d₆) δ: 9.53-9.45 (m, 1H), 8.57 (s, 1H), 7.29(d, J=12.1 Hz, 2H), 4.94-4.87 (m, 1H), 4.71 (s, 2H), 4.16-4.07 (m, 1H),3.93-3.75 (m, 7H); Mp: 199° C.

[0448] Examples 117-175 have been prepared by a person skilled in theart according to the methodology as described in the above Example 116.Example No. Structure Analytical Data 117

¹HNMR(200MHz, DMSO-d₆) δ: 9.53-9.45 (m, 1H), 8.57(s, 1H), 7.29(d,J=12.1Hz, 2H), 4.94-4.87(m, 1H), 4.71 (s, 2H), 4.16-4.07(m, 1H),3.93-3.75(m, 7H). 118

¹HNMR(200MHz, DMSO-d₆) δ: 9.53-9.45 (m, 1H), 8.57(s, 1H), 7.29(d,J=12.1Hz, 2H), 4.94-4.87(m, 1H), 4.71 (s, 2H), 4.16-4.07(m, 1H).393-3.75(m, 7H). 119

¹HNMR(CDCl₃, 200MHz): δ7.67-7.56 (m, 2H), 7.16(d, J=2.0 Hz, 1H),6.72(bs, 1H), 4.94(bs, 1H), 4.52(t, J=7.8Hz, 2H), 4.12-3.83 (m, 9H). Mp:137° C. 120

¹HNMR(CDCl₃, 200MHz): δ7.66-7.50 (m, 2H), 7.15(d, J=7.4 Hz, 1H),6.66(hump, 1H), 4.94(bs, 1H), 4.56-4.43(m, 4H), 4.12-3.84 (m, 6H),1.32(t, J=6.8 Hz, 3H). Mp: 208° C. 121

¹HNMR (CDCl₃+DMSO-d⁶, 200MHz): δ8.45(bs, 1H), 7.65-7.46(m, 2H), 7.17(d,J=8.8Hz, 1H), 4.81(bs, 1H), 4.53(t, J=7.4Hz, 2H), 4.09-3.99 (m, 3H),3.84-3.55(m, 3H), 3.13(q, J=10.4Hz, 2H). Mp: 184° C. 122

¹HNMR(DMSO-d⁶, 200MHz): δ9.54(m, 1H), 7.57(s, 4H), 4.90-4.80(m, 2H),4.44(t, J=7.4Hz, 2H), 4.21-4.01 (m, 4H), 3.88-3.77(m, 3H), 3.56-3.53(m,1H), 1.23-0.97(m, 6H). Mp: 153° C. 123

¹HNMR(CDCl₃, 200MHz): δ8.2(m, 1H), 7.7(d, J=10.74Hz, 1H), 7.5(t, 1H),7.3(d, J=8.79Hz, 1H), 5.0(m, 1H), 4.70(t, 2H), 4.1(m, 9H). Mp: 197° C.124

¹HNMR(CDCl₃, 200MHz): δ7.02(dd, J=2.4Hz and 12.8Hz, 1H), 7.49(t, J=8.8Hzand 12.8Hz, 1H), 7.20(dd, J=2.4Hz and 12.8Hz, 1H), 6.63(bs, 1H), 4.93(m, 1H), 4.54-4.44(q, J=7.4Hz, 2H), 4.13-3.72 (m, 8H), 3.24(s, 3H),1.32(t, J=7.0Hz, 3H). Mp: 197° C. 125

¹HNMR(CDCl₃, 200MHz): δ7.62(dd, J=2.4Hz and 12.6Hz, 1H), 7.49(t,J=8.8Hz, 1H), 7.20(dd, J=2.4Hz and 12.6Hz, 1H), 6.65(bs, 1H), 4.94(m,1H), 4.38 (t, J=8.8Hz, 2H), 4.13-3.73(m, 8H), 3.24(s, 3H), 1.78-1.63(m,2H), 0.99(t, 3H). Mp: >200° C. 126

¹HNMR(CDCl₃, 200MHz): δ7.62(dd, J=2.4Hz and 12.7Hz, 1H), 7.49(t,J=8.8Hz, 1H), 7.20(dd, J=2.4Hz and 12.7Hz, 1H), 6.70(bs, 1H), 4.94(m,1H), 4.13-3.72(m, 11H), 3.24(s, 3H). Mp: 179° C. 127

¹HNMR(CDCl₃, 200MHz): δ7.62(dd, J=2.4Hz and 12.7Hz, 1H), 7.49(t,J=8.8Hz, 1H), 7.20(dd, J=2.4Hz and 13.0Hz, 1H), 6.55(bs, 1H),5.58-5.49(heptet, 1H), 4.92(m, 1H), 4.13-3.73(m, 8H), 3.24(s, 3H),1.39-1.25(m, 6H). Mp: 183° C. 128

¹HNMR(CDCl₃, 200MHz): δ7.9(m, 2H), 7.5(d, J=8.79Hz, 1H), 6.7(s, 1H),5.0(s, 1H), 4.5(t, 2H), 4.0(m, 9H). Mp: 146° C. 129

¹HNMR(CDCl₃, 200MHz): δ7.8(m, 2H), 7.4(d, J=8.79Hz, 1H), 6.7(s, 1H),5.0(s, 1H), 4.5(m, 4H), 4.0(m, 6H), 1.3(m, 3H). Mp: 157° C. 130

¹HNMR(CDCl₃, 200MHz): δ7.29-7.24 (m, 2H), 6.73(hump, 1H), 4.96(huimp,1H), 4.58(t, J=7.4Hz, 2H), 4.08-3.83(m, 9H). Mp: 182° C. 131

¹HNMR(CDCl₃, 200MHz): δ7.52(s, 4H), 6.81(bs, 1H), 4.91 (hump, 1H),4.49(t, J=7.8Hz, 2H), 4.13-3.82 (m, 9H). Mp: 153° C. 132

¹HNMR(CDCl₃, 200MHz): δ7.5(s, 4H), 6.7(s, 1H), 4.9(s, 1H), 4.5(m, 4H),4.0(m, 6H), 1.3(t, J=6.8Hz, 3H). Mp: 168° C. 133

¹HNMR(CDCl₃, 200MHz): δ7.54(s, 4H), 6.7(s, 1H), 4.9(m, 1H), 4.4(m, 4H),4.0(m, 6H), 1.7(m, 2H), 0.95(t, J=7.4Hz, 3H). Mp: 176° C. 134

¹HNMR(CDCl₃, 200MHz): δ7.52(s, 4H), 7.26(bs, 1H), 4.96-4.77 (m, 3H),4.50(t, J=7.2 Hz, 2H), 4.15-3.80(m, 6H). Melting Point(° C.): 181 ° C.135

¹HNMR(CDCl₃, 200MHz): δ9.2-8.9(m, 1H), 7.5(s, 4H), 5.0-4.8 (m, 1H),4.6-4.4(m, 4H), 4.2-3.5(m, 8H). Mp: 141° C. 136

¹HNMR(CDCl₃, 200MHz): δ7.54(s, 4H), 6.81(bt, 1H), 4.91(m, 1H),4.67-4.58(m, 2H), 4.50(t, J=7.2Hz, 2H), 4.13-3.82(m, 6H), 3.68-3.63(m,2H), 3.38(s, 3H). Mp: 149° C. 137

¹HNMR(CDCl₃, 200MHz): δ7.55(s, 4H), 7.26(s, 2H), 6.7(s, 1H), 5.93(m,1H), 5.29(m, 2H), 4.9(m, 3H), 4.5(t, J=7.4Hz, 2H), 4.0(m, 6H). Mp: 150°C. 138

¹HNMR(CDCl₃, 200MHz): δ7.54(s, 4H), 6.57(s, 1H), 5.5(m, 1H), 4.92(m,1H), 4.5(t, J=7.4Hz, 2H), 4.0(m, 6H), 1.31(dd, J=10.2Hz and 13.8Hz, 6H).Mp: 140° C. 139

¹HNMR(CDCl₃, 200MHz): δ7.72(d, J=9.2Hz, 2H), 7.57(d, J=9.2Hz, 2H),7.31-7.01 (m, 4H), 6.77(bs, 1H), 4.97-4.96(m, 1H), 4.19-3.91(m, 7H). Mp:141° C. 140

¹HNMR(CDCl₃, 200MHz): δ7.73(d, J=8.8Hz, 2H), 7.56(d, J=8.8Hz, 2H),7.31-7.01 (m, 4H), 6.70(bs, 1H), 4.97(m, 1H), 4.55-4.44 (q, J=6.8Hz,2H), 4.19-3.92(m, 4H), 1.32(t, J=7.0Hz, 3H). Mp: 147° C. 141

¹HNMR(CDCl₃, 200MHz): δ2.8(s, 3H), 4.8(t, 1H), 3.6(m, 8H), 6.8(t, 1H),7.2(d, 1H), 7.5(dd, 1H). Mp: 218° C. 142

¹HNMR(CDCl₃, 200MHz): δ1.5(s, 3H), 2.9(s, 3H), 3.6(t, 2H), 4.9(m, 1H),6.8(m, 1H), 7.8(d, 2H). Mp: 209° C. 143

¹HNMR(DMSO-d⁶, 200MHz): 9.5(br, 1H), 7.4(d, J=8.8Hz, 2H), 6.6 (d,J=8.8Hz, 2H), 4.90-4.80(m, 1H), 4.7(s, 2H), 4.2-3.4(m, 9H), s, 3H). Mp:205° C. 144

¹HNMR(CDCl₃, 200MHz): δ7.5(m, 2H), 7.1(m, 1H), 6.9(s, 1H), 4.9(m, 1H),3.8(m, 9H), 3.4(t, J=8.8Hz, 2H), 2.9(s, 3H). Mp: 146° C. 145

¹HNMR(CDCl₃, 200MHz): δ7.6-7.2(m, 9H), 6.7(bt, 1H), 5.0-4.8 (m, 1H),4.5(s, 2H), 4.2-3.6(m, 9H), 3.4(t, J=8.8 Hz, 2H). Mp: 170° C. 146

¹HNMR(CDCl₃, 200MHz): δ7.6-7.2(m, 9H), 6.7(bt, 1H), 5.0-4.8 (m, 1H),4.6-4.4(m, 4H), 4.2-3.6(m, 6H), 3.7(t, J=8.3Hz, 2H), 1.3(t, J=6.8Hz,3H). Mp: 160° C. 147

¹HNMR(CDCl₃, 200MHz): δ9.5(m, 1H), 7.6(m, 4H), 7.4(m, 3H), 7.0(m, 1H),4.9(m, 1H), 4.2(m, 1H), 3.8-4.0(m, 7H), 3.3(s, 3H). 148

¹HNMR(CDCl₃, 200MHz): δ9.5(m, 1H), 7.6(m, 4H), 7.3(m, 3H), 7.1(t, 1H),4.8(m, 1H), 4.4(m, 2H), 4.2(m, 1H), 3.7-4.1(m, 5H), 3.5(m, 2H), 1.2(t,3H). Mp: 195° C. 149

¹HNMR(CDCl₃, 200MHz): δ7.5(m, 4H), 7.0(m, 4H), 4.9(m, 1H), 4.0(11H). Mp:208° C. 150

¹HNMR(CDCl₃, 200MHz): δ7.6(m, 4H), 7.0-7.2(m, 3H), 4.9(m, 2H), 4.5(m,2H), 4.0(m, 8H), 1.3(t, 3H). Mp: 215° C. 151

¹HNMR(CDCl₃, 200MHz): δ7.5(m, 4H), 7.0(m, 3H), 5.5(m, 1H), 4.9(m, 1H),4.0(m, 8H), 1.3(t, 6H). Mp: 220° C. 152

¹HNMR(DMSO-d⁶, 200 MHz): δ9.60-9.40(m, 1H), 7.57(s, 4H), 5.00-4.75(m,1H), 4.44-3.40 (m, 12H), 2.16(s, 6H). Mp: 161° C. 153

¹HNMR(CDCl₃, 200 MHz): δ7.40(dd, J=17.6, 2.4Hz, 1H), 7.24 (d, J=9.7Hz,2H), 7.04 (d, J=8.8Hz, 1H), 6.89 (d, J=8.8Hz, 2H), 6.78 (bt, 1H),6.58-6.49(m, 1H), 5.00-4.80(m, 1H), 4.75(s, 2H), 4.54(s, 2H),4.20-3.60(m, 9H), 3.81 (s, 3H). 154

¹HNMR(DMSO-d⁶, 200 MHz): δ9.50-9.35(m, 1H), 7.60-6.60(m, 8H),5.50-5.30(m, 1H), 4.95-4.70(m, 1H), 4.74(s, 2H), 4.55(s, 2H),4.20-3.25(m, 6H), 1.40-1.10 (bd, 6H). Mp: 192° C. 155

¹HNMR(DMSO-d⁶, 200 MHz): δ9.55-9.35(m, 1H), 7.45(d, J=18.1Hz, 1H),7.15(d, J=8.8Hz, 1H), 6.90-6.80(m, 1H), 6.09(t, J=6.8Hz, 1H), 4.87(s,2H), 4.90-4.75 (m, 1H), 4.71(d, J=6.8 Hz, 2H), 4.20-3.10(m, 9H). Mp:184° C. 156

¹HNMR(200 MHz, DMSO-d₆) δ: 11.10(bs, 1H), 9.55(m, 1H), 7.47 (d,J=15.6Hz, 1H), 7.17 (d, J=8.3Hz, 1H), 6.87 (t, J=9.5Hz, 1H), 5.00 (bs,2H), 4.85(m, 1H), 4.30(bs, 2H), 4.15-3.40 (m, 7H). 157

¹HNMR(200 MHz, DMSO-d₆) δ: 9.55(bs, 1H), 7.41(d, J=8.3Hz, 2H), 6.64(d,J=8.8Hz, 2H), 6.13(t, 1H), 4.79-4.75(m, 5H), 3.93-3.76 (m, 9H). MP:202-208° C. 158

¹HNMR(200 MHz, DMSO-d₆) δ: 9.50(bs, 1H), 8.64(s, 1H), 7.34 (d, J=8.6Hz,2H), 6.56 (d, J=8.6Hz, 2H), 4.60 (s, 3H), 3.88-3.67(m, 9H). MP: 205-210°C. 159

¹HNMR(200 MHz, DMSO-d₆) δ: 9.55(bs, 1H), 7.32(d, J=12.1 Hz, 2H), 6.12(t,J=7.3Hz, 1H), 4.87(s, 3H), 4.72 (d, J=7.3Hz, 2H), 4.13-3.76(m, 9H). 160

¹HNMR(200 MHz, DMSO-d₆) δ: 9.55(bs, 1H), 7.52-7.43(m, 1H), 7.17(d,J=9.0Hz, 1H), 6.82(t, J=9.8Hz, 1H), 4.90-4.81(m, 3H), 4.15-3.73(m, 6H),3.34-3.28 (m, 6H), 1.59-1.09(m, 4H), 0.90(t, J=7.2Hz, 3H). MP: 122° C.161

¹HNMR(200 MHz, DMSO-d₆) δ: 7.45(dd, J_(2,3)=12.9Hz & J_(1,2)=2.4 Hz,1H), 7.07(d, J=8.9 Hz, 1H), 6.79-6.70(m, 1H), 6.59(t, J=9.1Hz, 1H),5.82-5.74(m, 1H), 5.35-5.26(m, 2H), 4.86 (s, 3H), 4.20-4.01(m, 11H). MP:86° C. 162

¹HNMR(200 MHz, DMSO-d₆) δ: 9.55(bs, 1H), 7.55(d, J=13.4 Hz, 2H), 7.44(s,1H), 6.83(t, 1H), 4.87(s, 3H), 4.11-3.76(m, 11H). 163

¹HNMR(200 MHz, DMSO-d₆) δ: 9.35(bs, 1H), 7.51(d, 1H), 7.08 (d, J=8.3 Hz,1H), 6.60 (t, 1H), 5.10-4.65(m, 3H), 4.20-3.45(m, 14H). 164

¹HNMR(200 MHz, DMSO-d₆) δ: 9.53(bs, 1H), 7.29(d, J=12.4 Hz, 2H),4.88-4.76(m, 3H), 4.15-4.06(m, 1H), 3.91-3.74(m, 8H), 2.81(s, 3H). 165

¹HNMR(400 MHz, DMSO-d₆) δ: 9.47(bs, 1H), 8.53(s, 1H), 4.94-4.71(m, 3H),4.35-4.22 (m, 2H), 4.14-4.08(m, 1H), 3.81-3.63(m, 4H), 3.52-3.45(m, 1H),1.71-1.60(m, 2H), 0.93-0.84 (m, 3H). MP: 186-188° C. 166

¹HNMR(400 Mhz, DMSO-d₆) δ: 9.42(t, J=5.4Hz, 1H), 8.51(s, 1H), 4.88(m,1H), 4.69(s, 2H), 4.44-4.35(m, 2H), 4.19-4.02(m, 2H), 3.79-3.68(m, 4H),3.49-3.46 (m, 1H), 3.37-3.33(m, 1H), 1.32-1.21(m, 3H). MP: 178-180° C.167

¹HNMR(400 MHz, DMSO-d₆) δ: 9.34(bs, 1H), 8.51(s, 1H), 7.29 (dd,J_(2,3)=10.3Hz & J_(1,2)=3.9Hz, 2H), 5.43-5.37 (m, 1H), 4.91-4.85(m,1H), 4.76-4.69(m, 2H), 4.19-4.03(m, 2H), 3.93-3.62(m, 4H), 1.25-1.17 (m,6H). MP: 176-178° C. 168

¹HNMR(200 MHz, DMSO-d₆) δ: 9.53(bs, 1H), 7.32(d, J=11.8Hz, 2H),4.90-4.80(m, 3H), 4.13-3.76(m, 8H), 3.33 (s, 3H), 1.43(s, 9H). 169

¹HNMR(400 MHz, DMSO-d₆) δ: 9.50(bs, 1H), 7.29(d, J=12.2Hz, 2H), 4.84(m,3H), 4.17-3.30(m, 14 H). 170

¹HNMR(200 MHz, DMSO-d₆) δ: 9.53(bs, 1H), 7.29(d, J=12.4Hz, 2H),4.88-4.76(m, 3H), 4.15-4.06(m, 1H), 3.91-3.74(m, 8H), 2.81(s, 3H). 171

¹HNMR(400 MHz, DMSO-d₆) δ: 9.47(bs, 1H), 8.53(s, 1H), 4.94-4.71(m, 3H),4.35-4.22 (m, 2H), 4.14-4.08(m, 1H), 3.81-3.63(m, 4H), 3.52-3.45(m, 1H),1.71-1.60(m, 2H), 0.93-0.84 (m, 3H). 172

¹HNMR(400 MHz, DMSO-d₆) δ: 9.42(t, J=5.4 Hz, 1H), 8.51(s, 1H), 4.88(m,1H), 4.69(s, 2H), 4.44-4.35(m, 2H), 4.19-4.02(m, 2H), 3.79-3.68(m, 4H),3.49-3.46 (m, 1H), 3.37-3.33(m, 1H), 1.32-1.21(m, 3H). 173

¹HNMR(200 MHz, DMSO-d₆) δ: 9.53(bs, 1H), 7.29(d, J=12.4 Hz, 2H),4.88-4.76(m, 3H), 4.15-4.06(m, 1H), 3.91-3.74(m, 8H), 2.81(s, 3H). 174

¹HNMR(400 MHz, DMSO-d₆) δ: 9.47(bs, 1H), 8.53(s, 1H), 4.94-4.71(m, 3H),4.35-4.22 (m, 2H), 4.14-4.08(m, 1H), 3.81-3.63(m, 4H), 3.52-3.45(m, 1H),1.71-1.60(m, 2H), 0.93-0.84 (m, 3H). 175

¹HNMR(400 MHz, DMSO-d₆) δ: 9.42(t, J=5.4Hz, 1H), 8.51(s, 1H), 4.88(m,1H), 4.69(s, 2H), 4.44-4.35(m, 2H), 4.19-4.02(m, 2H), 3.79-3.68(m, 4H),3.49-3.46 (m, 1H), 3.37-3.33(m, 1H), 1.32-1.21(m, 3H).

[0449] K. General procedure for the conversion of

[0450] where R¹ is as defined for formula (I), where ‘Ar’ representssubstituted or unsubstituted phenyl ring, the substituents are asdefined on the phenyl ring of the formula (I).

[0451] Sodium hydride (360 mg, 7.5 mmol) was added to a solution ofstarting material (300 mg, 0.75 mmol) in dry THF (30 mL) and theresultant suspension was stirred at room temperature overnight. Thereaction mixture was diluted with ethyl acetate (150 mL) and washed withwater, brine and dried. The residue obtained upon evaporation of solventwas passed through a column of silica gel to afford the product as acolorless solid (150 mg, 54% yield).

[0452] Example 176 has been prepared by a person skilled in the artaccording to the methodology as described in the above Procedure K.Example No. Structure Analytical Data 176

¹HNMR(DMSO-d⁶, 200 MHz): δ9.60-9.40(m, 1H), 8.62(s, 1H), 7.45(d,J=16.2Hz, 1H), 7.16(d, J=8.6Hz, 1H), 6.90-6.80(m, 1H), 4.90-4.75(m, 1H),4.73(s, 2H), 4.20-3.40(m, 9H). Mp: 223° C.

[0453] L. General procedure for the conversion of

[0454] where R¹ is as defined for formula (I), where ‘Ar’ representssubstituted or unsubstituted phenyl ring, the substituents are asdefined on the phenyl ring of the formula (I); and R^(b) represents(C₁-C₁₀)alkyl or aralkyl.

[0455] To a solution of starting material (1 eq) in dry DMF was addedNaH (1.2 eq) at 0° C. under argon followed by appropriate alkyl halideor aralkyl halide (1.2 eq). The reaction mixture was stirred for 2-6 hwhile monitoring by TLC. After the consumption of starting material, thereaction mixture was diluted with ethyl acetate and washed with water,brine and dried. The residue obtained upon evaporation of solvent waspassed through a column of silica gel to afford the product.

[0456] Examples 177-180 have been prepared by a person skilled in theart according to the methodology as described in the above procedure L.Example No. Structure Analytical Data 177

¹HNMR(DMSO-d⁶, 200 Mhz): δ9.60-9.40(m, 1H), 7.49(dd, J=15.6, 2.4 Hz,1H), 7.18(d, J=9.1 Hz, 1H), 6.95-6.80(m, 1H), 5.17 (s, 2H), 4.95-4.70(m,1H), 4.42(s, 2H), 4.20-3.40(m, 7H). Mp: 195° C. 178

¹HNMR(CDCl₃, 200 MHz): δ7.46(dd, J=15.1, 2.4 Hz, 1H), 7.10(d, J=8.8Hz,1H), 6.77(bt, 1H), 6.65-6.56(m, 1H), 4.97(s, 2H), 4.97-4.80 (m, 1H),4.84(s, 2H), 4.20-3.55(m, 9H), 3.37 (s, 3H). Mp: 160° C. 179

¹HNMR(CDCl₃+DMSO-d⁶, 200 MHz): δ9.95-9.25(m, 1H), 7.55-7.25(m, 6H),7.45(d, J=15.4 Hz, 1H), 6.63-6.54(m, 1H), 5.00-4.80 (m, 1H), 4.77(s,2H), 4.60(s, 2H), 4.20-3.75 (m, 9H). Mp: 176° C. 180

¹HNMR(CDCl₃, 200 MHz): δ7.50-7.20(m, 6H), 7.04(d, J=8.6 Hz, 1H),6.78(bt, 1H), 6.58-6.49 (m, 1H), 5.00-4.35(m, 7H), 4.20-3.60(m, 6H),1.31(t, J=7.0Hz, 3H). Mp: 184° C.

[0457] M. General procedure for the conversion of

[0458] where ‘Ox’ represents a five membered heterocyclic group,containing at least one nitrogen atom and one more heteroatom selectedfrom oxygen, nitrogen or sulfur. In which, the said atleast one nitrogenatom connecting said heterocyclic moiety ‘Ox’ to the ‘Ar’ moiety. Theheterocyclic moiety is substituted by an ═O or ═S. The heterocycle mayalso be substituted by one or two additional substituents which are asdefined on the heterocyclic moiety of formula (I). The heterocycle mayalso be fused with substituted or unsubstituted phenyl group. ‘Ar’represents substituted or unsubstituted phenyl ring, the substituentsare as defined on the phenyl ring of the formula (I); R′ representshydrogen, alkyl, alkenyl, substituted or unsubstituted aralkyl,heteroaralkyl, hydroxyalkyl and R″ represents hydrogen or alkyl; or thetwo R′ and R″ groups together form a 5 or 6 membered cyclic structurescontaining one or two hetero atoms.

Reference Example of the Above Preparation Example 181(S)-1-{3-[3,5-Difluoro-4-(4-oxo-imidazolidin-1-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-3-pyridin-2-yl-thiourea

[0459]

[0460] 2-Amino pyridine (32 mg. 0.34 mmol) was added to a solution ofisothiocyanate (100 mg, 0.3 mmol), obtained in step (i) of the example116, in THF at 20 to 35° C. The resultant mixture was reflusedovernight. The residue obtained upon evaporation of the solvent waspassed through a column of silica gel to afford the title compound(Yield: 50 mg, 40%).

[0461]¹H NMR (400 MHz, DMSO-d₆) δ: 11.99 (t, J=5.5 Hz, 1H), 10.71 (s,1H), 8.51 (s, 1H), 8.11 (dd, J_(2,3)=5.1 Hz & J_(1,2)=1.6 Hz, 1H), 7.76(m, 1H), 7.13 (d, J=8.2 Hz, 2H), 7.03 (m, 1H), 5.05-5.02 (m, 1H), 4.68(s, 2H), 4.18-4.01 (m, 3H), 3.85-3.78 (m, 3H); Mp: 194-196° C.

[0462] Examples 182-195 have been prepared by a person skilled in theart according to the methodology as described in the above Example 181.Example No. Structure Analytical Data 182

¹HNMR(CDCl₃, 200MHz): δ7.51 (s, 4H), 4.98-4.95(m, 1H), 4.49(t, J=7.8 HZ,2H), 4.17-3.88(m, 8H), 3.71-3.69(m, 3H), 1.93-1.78(m, 4H). Mp: 159° C.183

¹HNMR(DMSO-d⁶, 200MHz): δ7.63(s, 1H), 7.57(s, 4H), 4.94-4.91 (m, 1H),4.44(t, J=7.4 Hz, 2H), 4.17-3.75(m, 6H), 3.66-3.56(q, J J=6.8 Hz, 4H),1.07(t, J=6.8 Hz, 6H). Mp: 103° C. 184

¹HNMR(DMSO-d⁶, 200MHz): δ7.79(bs, 1H), 7.57(s, 4H), 5.80-5.75(m, 1H),5.15-5.01(m, 2H), 4.86(m, 1H), 4.44(t, J=7.4 Hz, 2H), 4.17-4.01 (m, 5H),3.85(m, 2H). Mp: 171° C. 185

¹HNMR(DMSO-d⁶, 200MHz): δ8.05(bs, 1H), 7.86(bs, 1H), 7.57(s, 4H),7.25(s, 5H), 4.88-4.84(m, 1H), 4.67(s, 2H), 4.44(t, J=7.8 Hz, 2H),4.16-4.01(m, 3H), 3.89-3.86(m, 3H). Mp: 181° C. 186

¹HNMR(DMSO-d⁶, 200MHz): δ8.00(bs, 1H), 7.80(bs, 1H), 7.57(s, 4H),7.19-7.15(d, J=8.4 Hz, 2H), 6.84-6.80(d, J=8.2 Hz, 2H), 4.86 (bs, 1H),4.57(bs, 2H), 4.44(t, J=7.4 Hz, 2H), 4.08-4.01(m, 3H), 3.88-3.85(m, 3H),3.70(s, 3H). Mp: 169°O C. 187

¹HNMR(DMSO-d⁶, 200MHz): δ8.50-8.48(d, J=3.8 Hz, 1H), 8.16 (m, 2H),7.69(t, J=7.8 Hz, 1H), 7.57 (s, 4H), 7.26-7.22 (d, J=7.8 Hz, 2H),4.88(m, 1H), 4.75(bs, 2H), 4.44(t, J=7.2 Hz, 2H), 4.18-4.01(m, 3H),3.89-3.82(m, 3H). Mp: 165° C. 188

¹HNMR(DMSO-d⁶, 200MHz): δ7.77(bs, 1H), 7.57(s, 5H), 4.86(m, 1H), 4.44(t,J=7.8 Hz, 2H), 4.17-4.01(m, 3H), 3.81-3.33(m, 3H), 2.83(bs, 3H). Mp:175° C. 189

¹HNMR(DMSO-d⁶, 200MHz): δ7.86(hump, 1H), 7.66(hump, 1H), 7.57(s, 4H),4.78-4.68(m, 2H), 4.43 (t, J=7.2 Hz, 2H), 4.12-4.01(m, 3H), 3.83(bs,3H), 3.46-3.33(m, 4H). Mp: 161° C. 190

¹HNMR(DMSO-d⁶, 200MHz): δ8.05(hump, 1H), 7.57(s, 4H), 4.95 (m, 1H),4.43(t, J=7.2 Hz, 2H), 4.08-3.89(m, 8H), 2.57(s, 4H), 2.49 (s, 4H). Mp:159° C. 191

¹HNMR(DMSO-d⁶, 200MHz): δ12.06(bs, 1H), 10.76(s, 1H), 8.14-8.11(d,J=5.0Hz, 1H), 7.77(t, J=8.2 Hz, 1H), 7.52(s, 4H), 7.17-7.13(d, J=3.2 Hz,1H), 7.04(t, J=5.8 Hz, 1H), 5.05-5.03(m, 1H), 4.43(t, J=7.4 Hz, 2H),4.22(t, J=9.2 Hz, 1H), 4.07-3.84(m, 5H). Mp: 189° C. 192

¹HNMR(CDCl₃+DMSO-d^(6, 200MHz): δ8.07(bs, 1H), 7.62-7.40 (m, 2H), 7.16(d, J=7.8 Hz, 1H), 6.65(bs, 1H), 4.85(bs, 1H), 4.48(t, J=8.0 Hz, 2H), 4.04-3.96(m, 6H). Mp: 178° C.)193

¹HNMR(CDCl₃+DMSO-d^(6, 200MHz): δ7.68-7.19(m, 5H), 4.92 (hump, 1H), 4.53(t, J=7.8 Hz, 2H), 4.08-3.98(m, 6H), 3.10(s, 3H). Mp: 144° C.)194

¹HNMR(CDCl+DMSO-d⁶, 200MHz): δ8.10(bs, 1H), 7.35(d, J=8.4 Hz, 2H),6.58(bs, 1H), 4.91-4.89(m, 1H), 4.58(t, J=7.8 Hz, 2H), 4.54-3.87(m, 6H).Mp: 92° C. 195

¹HNMR(CDCl₃, 200MHz): δ7.26(s, 2H), 6.39(hump, 2H), 4.93(hump, 1H),4.60(t, J=7.4 Hz, 2H), 4.21-3.93(m, 6H), 2.99(d, J=4.8Hz, 3H). Mp: 113°C.

Example 196(S)-(3-{2,6-Difluoro-4-[5-(methoxythiocarbonylamino-methyl)-2-oxo-oxazolidin-3-yl]-phenyl}-5-oxo-imidazolidin-1-yl)-aceticAcid

[0463]

[0464] A solution of dioxane presaturated with dry HCl gas (2 mL) wasadded to a solution of compound (100 mg, 0.2 mmol), obtained in example168, in dry dioxane (5 mL) at room temperature. The reaction mixture wasstirred at room temperature for 15 h and then the mixture wasconcentrated at high vacuum pump. The residue obtained was washed a fewtimes with toluene and the crystals were washed with ether to obtain theproduct.

[0465]¹H NMR (400 MHz, DMSO-d₆) δ: 12.93 (bs, 1H), 9.42 (bs, 1H), 7.31(m, 2H), 4.88 (m, 3H), 4.15-3.20 (m, 11H).

Example 197(S)-{3-[3,5-Difluoro-4-(3-methyl-4-oxo-imidazolidin-1-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-methyl-thiocarbamicAcid O-methyl Ester

[0466]

[0467] Sodium hydride (11 g, 60% in oil, 0.3 mmol) was added to asolution of the starting material (100 mg, 0.3 mmol), obtained inexample 164, in dry DMF at room temperature. After stirring for afurther 30 min, methyliodide (0.0.24 mmol, 0.4 mmol) was added and thereaction was continued for an additional 2 h. The reaction mixture wasextracted with ethyl acetate after quenching with aq. NH₄Cl. The organicextracts were washed with water, brine and dried. The residue was passedthrough column to afford the title compound (40 g). Prolonged columnafforded the 20 g of the title compound.

[0468]¹H NMR (200 MHz, DMSO-d₆) δ: 7.33 (d, J=12.4 Hz, 2H), 4.90-4.78(m, 3H), 4.11 (t, J=8.9 Hz, 1H), 3.91 (s, 2H), 3.84-3.77 (m, 1H), 3.60(s, 3H), 3.41-3.33 (m, 3H), 2.50 (s, 2H), 2.38 (s, 3H); Mp: 130° C.

[0469] Example 198 has been prepared by a person skilled in the artaccording to the methodology as described in the above Example 197. 198

¹HNMR(400 MHz, DMSO-d₆)δ: 8.56(s, 1H), 7.32(dd, J_(2,3)=18.1 Hz &J_(1,2)=5.8 Hz, 2H), 4.91-4.86(m, 1H), 4.71(s, 2H), 4.11(t, J=8.8Hz,1H), 3.81(s, 3H), 3.60(s, 3H), 3.42 (d, J=3.9 Hz, 1H), 3.41(d, J=3.9 Hz,1H), 3.36(t, J=3.9 Hz, 1H), 2.39(s, 2H). MP: 154-156° C.

Example 199N1-((5S)-3-{3-Fluoro-4-[3-benzyl-4-oxo-1-imidazolidinyl]phenyl}-2-oxo-1,3-oxazolan-5-ylmethyl)ethylthiocarbamateHydrochloride

[0470]

[0471]N1-((5S)-3-{3-fluoro-4-[3-benzyl-4-oxo-1-imidazolidinyl]phenyl}-2-1,3-oxazolan-5-ylmethyl)ethylthiocarbamate,obtained in example 152, was taken in methanol (100 mg) and was bubbledwith HCl gas for 30 min. Then methanol was evaporated from the resultantmixture and washed with ether twice to obtain the title compound (Yield:100%). Mp: 100° C. (hygroscopic).

[0472]¹H NMR (DMSO-d⁶, 200 MHz): δ 10.60 (bs, 1H), 9.85-9.65 (m, 1H),7.58 (s, 4H), 5.00-4.65 (m, 3H), 4.44 (t, J=7.6 Hz, 2H), 4.25-3.40 (m,8H), 2.81 (s, 3H), 2.79 (s, 3H).

[0473] In vitro Data:

[0474] Minimum Inhibiton Concentrations (MICs) were determined by brothmicrodilution technique as per the guidelines prescribed in the fifthedition of Approved Standards, NCCLS document M7-A5 Vol 20-No 2, 2000Villinova, Pa.

[0475] Initial stock solution of the test compound was prepared in DMSO.Subsequent two fold dilutions were carried out in sterile Mueller HintonBroth (Difco) (MHB).

[0476] Frozen cultures stocks were inoculated into 50 ml sterile MHB in250 ml Erlyn Meyer flasks.

[0477] Composition of MHB is as follows:

[0478] Beef Extract Powder—2.0 g/litre

[0479] Acid Digest of Casein—17.5 g/litre

[0480] Soluble Starch—1.5 g/litre

[0481] Final pH 7.3±0.1

[0482] Flasks were incubated for 4 to 5 h at 35° C. on a rotary shakerat 150 rpm. Inoculum was prepared by diluting the culture in sterile MHBto obtain a turbidity of 0.5 McFarland standard. This corresponds to1-2×10⁸ CFU/ml. The stock was further diluted in sterile broth to obtain1-2×10⁶ CFU/ml. 50 μl of the above diluted inoculum was added from 1-10wells. The plates were incubated overnight at 37° C.

[0483] MIC is read as the lowest concentration of the compound thatcompletely inhibits growth of the organism in the microdilution wells asdetected by the unaided eye. Organism Culture No. DRCC No.Staphylococcus aureus ATCC 33591 019 Staphylococcus aureus ATCC 49951213 Staphylococcus aureus ATCC 29213 035 Enterococcus faecalis ATCC29212 034 Enterococcus faecalis NCTC 12201 153 Enterococcus faecium NCTC12202 154 Escherichia coli ATCC 25922 018 Haemophilus influenzae ATCC49247 432 Haemophilus influenzae ATCC 49766 433 Haemophilus influenzaeATCC 9006 529 Moraxella catarrhalis ATCC 25238 300 Streptococcuspneumoniae ATCC 6303 236 Streptococcus pneumoniae ATCC 49619 237Streptococcus pneumoniae ATCC 700673 238 S. aureus - MRSA and QRSA — 446S. aureus - MRSA and QRSA — 448 S. aureus - MRSA and QRSA — 449Corynebacterium jeikeium Viridans Streptococci

[0484] TABLE 1 In vitro Activity of Compounds against Gram positive andGram negative bacteria Antimicrobial Screening (MIC) μg/mlStaphylococcus aureus Enterococcus sp M. Example 019 213 035 034 153 154Mycobacterium Salmorella catarrhalis H. influenzae No. MRSA Smith S S SR R MTCC 006 TA 97 300 432 433 529 164 0.25 0.5 0.5 0.5 0.5 0.5 4 16 8 816 16 165 1 1 1 2 2 2 32 32 >32 >32 >32 >32 166 0.5 0.5 0.5 1 1 1 32 3232 >32 >32 >32 167 2 2 2 8 4 8 32 32 >32 >32 >32 >32 168 2 2 2 2 1 2 3232 — — — — 169 1 1 2 0.5 0.5 1 8 32 — — — —

1. A compound that is an oxazolidinone derivative of the formula (I)

or a salt thereof, or a stereoisomer thereof, where R¹ represents —NHR⁴wherein R⁴ represents thio(C₁-C₁₀)acyl, —C(═S)-cyclo(C₃-C₈)alkoxy,—C(═S)—(C₁-C₁₀)alkoxy, —C(═S)—(C₂-C₁₀)alkenyloxy, —C(═S)-aryloxy,(C═S)—S—(C₁-C₁₀)alkyl, —(C═S)—NH₂, —(C═S)—NH—(C₁-C₁₀)alkyl,—C(═S)—N—((C₁-C₁₀)alkyl)2, —C(═S)—NH—(C₂-C₁₀)alkenyl,(C═S)—(C═O)—(C₁-C₁₀)alkoxy, —(C═S)—(C═O)-aryloxy,—C(═S)—O—(C═O)—(C₁-C₁₀)alkyl, C(═S)—C(═S)—(C₁-C₁₀)alkyl,—C(═S)—C(═S)-aryl, —C(═S)-thiomorpholinyl or —C(═S)-pyrrolidinyl; R² andR³, which may be the same or different, are each independently hydrogen,halogen, (C₁-C₁₀)alkyl, halogenated (C₁-C₁₀)alkyl, cyano, nitro, SR^(a),NR^(a), or OR^(a), in which R^(a) is hydrogen, (C₁-C₁₀)alkyl orhalogenated (C₁-C₁₀)alkyl;

is a heterocyclic moiety in which

is a 5-membered heterocyclic skeleton, Z represents O, S, ═CH, —CH₂ orNR^(b), where R^(b) is hydrogen or a moiety, which may be substituted orunsubstituted, straight chain or branched, selected from the groupconsisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, (C₃-C₈)cycloalkyl,hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy, (C₁-C₁₀)alkylamino,amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl, aryloxy,(C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀) alkoxycarbonyl andaryloxycarbonyl; Y¹ represents ═O or ═S group and Y² and Y³independently represent hydrogen, halogen, cyano, nitro, formyl,hydroxy, amino, ═O, ═S group or substituted or unsubstituted groupsselected from (C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyl,(C₁-C₁₀)alkoxycarbonyl, arylcarbonyl, carboxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylsulfonyl, (C₁-C₁₀)alkylcarbony(C₁-C₁₀)alkyl,arylcarbonylamino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyloxy(C₁-C₁₀)alkyl,amino(C₁-C₁₀)alkyl, mono(C₁-C₁₀)alkylamino, di(C₁-C₁₀)alkylamino,arylamino, (C₁-C₁₀)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl or heterocycloalkyl; Y² and Y³ when presenton adjacent carbon atoms together may also form a substituted orunsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure,optionally containing one or two hetero atoms selected from oxygen,sulfur and nitrogen.
 2. The compound of claim 1 having the structure

wherein X¹ is oxygen or sulfur.
 3. The compound of claim 1 having thestructure

wherein X¹ is oxygen or sulfur.
 4. The compound of claim 1 having thestructure

wherein X¹ is oxygen or sulfur, and

is a substituted or unsubstituted 5- or 6-membered aromatic ornon-aromatic cyclic structure optionally having one or two hetero atoms,formed by Y² and Y³.
 5. The compound of claim 1 having the structure

wherein X¹ is oxygen or sulfur.
 6. The compound of claim 1 having thestructure

wherein X¹ is oxygen or sulfur.
 7. The compound of claim 4, wherein saidcyclic structure formed by Y² and Y³ is benzene, pyridine, pyrrolidine,furan, thiophene, morpholine, piperazine or pyrrole.
 8. The compound ofthe formula (I) as defined according to claim 1 which is selected from:


9. A compound that is an oxazolidinone derivative of the structure

or a salt thereof, or a stereoisomer thereof, where R^(N) is

wherein R^(b) is hydrogen or a moiety, which may be substituted orunsubstituted, straight chain or branched, selected from the groupconsisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, (C₃-C₈)cycloalkyl,hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy, (C₁-C₁₀)alkylamino,amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl, aryloxy,(C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀)alkoxycarbonyl, oraryloxycarbonyl; R⁷ represents hydrogen, (C₁-C₁₀)alkyl or(C₁-C₁₀)alkoxy; R² and R³, which may be same or different, are eachindependently hydrogen, halo, (C₁-C₁₀)alkyl, halogenated(C₁-C₁₀)alkyl,hydroxyl, (C₁-C₁₀)alkoxy or (C₁-C₁₀)alkylhydroxy; and R⁴ representshydrogen atom, or substituted or unsubstituted groups selected fromthio(C₁-C₁₀)acyl, —C(═S)—(C₁-C₁₀)alkoxy, —C(═S)—(C₂-C₁₀)alkenyloxy,—C(═S)-aryloxy, —(C═S)—S—(C₁-₁₀)alkyl, —(C═S)—NH₂,—(C═S)—NH—(C₁-C₁₀)alkyl, —C(═S)—N—((C₁-C₁₀)alkyl)₂,—C(═S)—NH—(C₂-C₁₀)alkenyl, (C═S)—(C═O)—(C₁-C₁₀)alkoxy,—(C═S)—(C═O)-aryloxy, —C(═S)—O—(C═O)—(C₁-C₁₀)alkyl,C(═S)—C(═S)—(C₁-C₁₀)alkyl, —C(═S)—C(═S)-aryl, —C(═S)-thiomorpholinyl or—C(═S)-pyrrolidinyl.
 10. The compound of claim 9, wherein R^(N) has thestructure

in which R^(b) is hydrogen, substituted or unsubstituted (C₁-C₁₀)alkyl,halogenated (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, (C₁-C₁₀)alkylhydroxy,hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylamino, amino(C₁-C₁₀)alkyl,halogenated(C₁-C₁₀)alkylhydroxy, (C₁-C₁₀)alkylamino, amino(C₁-C₁₀)alkylhalogenated(C₁-C₁₀)alkylhydroxy, the group of the structure

the group of the structure the group of the structure the group of thestructure the group of the structure

in which R′ is hydrogen, (C₁-C₁₀)alkyl or carboxy (C₁-C₁₀)alkyl; R⁶ ishydrogen, halo or (C₁-C₁₀)alkoxy and m is ranging from 1 to
 4. 11. Thecompound of claim 10, wherein R^(N) is


12. The compound of claim 11, wherein R^(b) is hydrogen or methyl. 13.The compound of claim 10 wherein R^(N) is selected from


14. The compound of claim 13, wherein R^(b) is hydrogen, methyl, benzyl,p-methoxybenzyl, n-butyl, propenyl or methylhydroxy.
 15. The compound ofclaim 13, wherein R^(b) has the structure


16. The compound of claim 10, wherein R^(N) is


17. The compound of claim 16, wherein R^(b) is methyl.
 18. The compoundof claim 10, wherein R^(N) is


19. The compound of claim 18, wherein R^(b) is methyl, benzyl,p-fluorobenzyl, p-fluorophenyl or phenyl.
 20. The compound of claim 10,wherein R^(b) has the structure

in which R⁶ is hydrogen, fluoro or methoxy group.
 21. The compound ofclaim 10, wherein R^(b) has the structure

where R⁶ is hydrogen, fluoro or methoxy group.
 22. The compound of claim9, wherein R^(N) is


23. The compound of claim 9, wherein R^(N) is


24. The compound of claim 9, wherein R^(N) has the structure

where R⁷ is hydrogen, (C₁-C₁₀)alkyl or (C₁-C₁₀)alkoxy.
 25. The compoundof claim 9, wherein R^(N) has the structure


26. The compound of claim 9, wherein R² and R³ are each independentlyhydrogen, fluoro or trifluoromethyl.
 27. The compound of claim 9,wherein R^(N) has the structure

in which R^(b) is hydrogen, substituted or unstubstituted (C₁-C₁₀)alkyl,halogenated (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, aralkyl,(C₁-C₁₀)alkylcarbonyl, (C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylhydroxy, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylamino,amino(C₁-C₁₀)alkyl, dihydroxy(C₁-C₁₀)alkyl, halogenatedhydroxy(C₁-C₁₀)alkyl, halogenated(C₁-C₁₀) alkylhydroxy; wherein R⁴ is—C(═S)—H, —C(═S)—(C₁-C₁₀)alkyl, —C(═S)—(C₁-C₁₀)alkoxy, —C(═S)—NH₂,—C(═S)-hydroxy(C₁-C₁₀)alkyl, —C(═S)-halogenated(C₁-C₁₀)alkyl,—C(═S)-phenyl; and R² and R³ are each independently hydrogen, fluoro ortrifluoromethyl group.
 28. The compound of claim 27, wherein R^(N) is


29. The compound of claim 27, wherein R^(N) has the structure

in which R^(b) is hydrogen, methyl, ethyl, propyl, n-butyl, benzyl,p-methoxybenzyl, hydroxy ethyl (ethylhydroxy), methoxyethyl, propenyl,

and R⁴ is C(═S)—CH₃. —C(═S)—OCH₃. —C(═S)—OCH₂CH₃. —C(═S)—(iso-propoxy)or —C(═S)—NH(pyridyl).
 30. The compound of claim 28 having the structure


31. The compound of claim 29 having the structure


32. The compound of claim 29 having the structure


33. The compound of claim 29 having the structure


34. The compound of claim 29 having the structure


35. The compound of claim 29 having the structure


36. The compound of claim 29 having the structure


37. The compound of claim 29 having the structure


38. The compound of claim 29 having the structure


39. The compound of claim 29 having the structure


40. The compound of claim 29 having the structure


41. The compound of claim 29 having the structure


42. The compound of claim 29 having the structure


43. The compound of claim 29 having the structure


44. The compound of claim 29 having the structure


45. The compound of claim 29 having the structure


46. The compound of claim 29 having the structure


47. The compound of claim 9, wherein R⁴ is —C(═S)—(C₁-C₁₀)akyl,—(═S)-halogenated(C₁-C₁₀)alkyl, —C(═S)—S—(C₁-C₁₀)akyl,—C(═S)—(C₁-C₁₀)alkoxy, —C(═S)—O—C(═O)—(C₁-C₁₀)alkyl,—C(═S)—(C₃-C₈)cycloalkoxy, —C(═S)—(C₂-C₁₀)alkenyloxy,—C(═S)-pyrrolidinyl, —C(═S)—NH₂, —C(═S)—N((C₁-C₁₀)alkyl)₂,—C(═S)—NH—(C₂-C₁₀)alkenyl, —C(═S)-thiomorpholinyl; R^(N) has thestructure

and R² and R³ are each independently hydrogen, fluoro or trifluoromethylgroup.
 48. The compound of claim 47, where in R⁴ is —C(═S)—CH₃,—C(═S)—CH₂—CH₃, —C(═S)—CH₂—CF₃, —C(═S)—S—CH₃, —C(═S)—O—CH₃,—C(═S)—O—CH₂—CH₃, —C(═S)—O—CH₂—CH₂—CH₃, —C(═S)—O-(iso-propyl),—C(═S)—O—CH₂—CF₃, —C(═S)—O-cyclohexyl, —C(═S)—O—CH₂—CH═CH₂,—C(═S)—CH₂—CH₂—N(CH₃)₂, —C(═S)—O—CH₂—CH₂OH, —C(═S)—CH₂—CH₂—OCH₃,—C(═S)—O—C(═O)—CF₃, —C(═S)—NH², —C(═S)—NH—CH₂, C(═S)—NH—CH₂—CH₂—OH,—C(═S)—N(CH₂CH₃)₂, —C(═S)—NH—CH₂—CH═CH₂, —C(═S)—NH-benzyl,—C(═S)—NH-pyridyl, —C(═S)—NH-(p-methoxybenzyl), —C(═S)—NH—CH₂-pyridyl,—C(═S)-thiomorpholinyl, —C(═S)—O—CH₂—CH₂—,N⁺HCl⁻, or


49. The compound of claim 48 having the structures


50. The compound of claim 48 having the structure


51. The compound of claim 48 having the structure


52. The compound of claim 48 having the structure


53. The compound of claim 1, 8 or 9, wherein said salt is apharmaceutically acceptable salt.
 54. The compound of claim 53, whereinsaid pharmaceutically-acceptable salt is a basic addition salt.
 55. Thecompound of claim 54, wherein said basic addition salt is selected fromthe group consisting of salts of Li, Na, K, Ca, Mg, Fe, Cu, Zn, Al andMn.
 56. The compound of claim 54, wherein said basic addition salt is asalt of a chiral base.
 57. The compound of claim 54, wherein said basicaddition salt is a salt of an organic base.
 58. The compound of claim 1,8 or 9, wherein said salt is a salt of guanidine, substituted guanidinesalts, ammonium, or substituted ammonium.
 59. The compound of claim 53,wherein said pharmaceutically-acceptable salt is an acid addition salt.60. The compound of claim 1, 8 or 9, wherein said salt is a salt of anatural amino acid, a synthetic amino acid, or a substituted aminoacids.
 61. The compound of claim 1, 8 or 9, which is optically active.62. The compound of claim 1, 8 or 9, which is racemic.
 63. A tautomericform of the compound of claim 1, 8 or
 9. 64. An in vivo hydrolysableprecursor of the compound of claims 1, 8 or
 9. 65. The in vivohydrolysable precursor of claim 64, which is an ester.
 66. The compoundof claim 53, wherein said salt of organic base is selected from thegroup consisting of salts of N,N′-diacetylethylenediamine, betaine,caffeine, 2-diethylaminoethanol, 2-dimethylaminoethanol,N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine,hydrabamine, isopropylamine, methylglucamine, morpholine, piperazine,piperidine, procaine, purines, theobromine, triethylamine,trimethylamine, tripropylamine, tromethamine, diethanolamine, meglumine,ethylenediamine, N,N′-diphenylethylenediamine,N,N′-dibenzylethylenediamine, N-benzyl phenylethylamine, choline,choline hydroxide, dicyclohexylamine, metformin, benzylamine,phenylethylamine, dialkylamine, trialkylamine, thiamine,aminopyrimidine, aminopyridine, purine, and spermidine.
 67. The compoundof claim 56, wherein said salt of chiral base is selected from the groupconsisting of salts of alkylphenylamine, glycinol, and phenyl glycinol.68. The compound of claim 60, wherein said natural amino acid isselected from the group consisting of glycine, alanine, valine, leucine,isoleucine, norleucine, tyrosine, cystine, cysteine, methionine,proline, hydroxy proline, histidine, omithine, lysine, arginine, serine,threonine, and phenylalanine.
 69. The compound of claim 59, wherein saidfrom acid addition salt is selected from sulphate, nitrate, phosphate,perchlorate, borate, halide, acetate, tartrate, maleate, citrate,succinate, palmoates, methanesulphonate, benzoate, salicylate,hydroxynaphthoate, benzenesulfonate, ascorbate, glycerophosphate, andketoglutarate.
 70. A method for inhibiting the growth of bacteria in asubject having a bacterial infection, which comprises administering tothe subject an amount of the compound of claim 1, 8, or 9 effective toinhibit the growth of the bacteria.
 71. The method according to claim70, wherein the bacterial infection is caused by the drug susceptible orresistance pathogens.
 72. The method according to claim 71, wherein drugresistance pathogens are selected from Methicillin-ResistantStaphylococcus Aureas (MRSA), streptococci, enterococci, anaerobicorganisms, Clostridia spp. species and acid-fast organisms.
 73. Themethod of claim 71, wherein said drug resistance pathogens are Strpneumoniae or Str pyogenes.
 74. The method of claim 71, wherein saiddrug resistance pathogen is Bacteroides spp.
 75. The method of claim 71,wherein said drug resistance pathogen is Mycobacterium tuberculosis,Mycobacterium avium and Mycobacterium spp. Fastidious Gram negativeorganisms, Hemophilus influenzae (H Influenzae) or Morexella catarrhalis(M Catarrhalis).
 76. The method of claim 70, wherein the bacterialinfection is caused by the Fluoroquinolone resitant bacteria, Macrolideresistant bacteria, Vancomycin resitatn bacteria and β-lactam resistantbacteria.
 77. The method of claim 70, further comprising administering asecond antibacterial agent in combination with the compound of claim 1,8 or 9 to said subject.
 78. The method of claim 77, wherein said secondantibacterial agent is selected from the group consisting of β-lactams,aminoglycosides, other oxazolidinones, linezolid, fluoroquinolines, andmacrolides.
 79. A pharmaceutical composition comprising a) anantibacterially effective amount of the compound of claim 1, 8, or 9;and b) a pharmaceutically acceptable carrier.
 80. The pharmaceuticalcomposition of claim 79, which is a tablet, a capsule, a powder, asyrup, a solution or a suspension.
 81. A process for the preparation ofcompound of formula (I)

where R¹ represents —NHR⁴, wherein R⁴ represents —C(═S)—R^(4b), whereinR^(4b) represents (C₁-C₁₀)alkyl, halo(C₁-C₁₀)alkyl,—C(═O)—(C₁-C₁₀)alkoxy, —C(═O)-aryloxy, —C(═S)—(C₁-C₁₀)alkyl or—C(═S)-aryl; R² and R³, which may be the same or different, are eachindependently hydrogen, halogen, (C₁-C₁₀)alkyl, halogenated(C₁-C₁₀)alkyl, cyano, nitro, SR^(a), NR^(a), or OR^(a), in which R^(a)is hydrogen, (C₁-C₁₀)alkyl or halogenated (C₁-C₁₀)alkyl;

is a heterocyclic moiety in which

is a 5-membered heterocyclic skeleton, Z represents O, S, ═CH, —CH₂ orNR^(b), where R^(b) is hydrogen or a moiety, which may be substituted orunsubstituted, straight chain or branched, selected from the groupconsisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, (C₃-C₈)cycloalkyl,hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy, (C₁-C₁₀)alkylamino,amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl, aryloxy,(C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀)alkoxycarbonyl andaryloxycarbonyl; Y¹ represents ═O or ═S group and Y² and Y³independently represent hydrogen, halogen, cyano, nitro, formyl,hydroxy, amino, ═O, ═S group or substituted or unsubstituted groupsselected from (C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy, (C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyl,(C₁-C₁₀) alkoxycarbonyl, arylcarbonyl, carboxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylsulfonyl, (C₁-C₁₀) alkylcarbony(C₁-C₁₀)alkyl,arylcarbonylamino(C₁-C₁₀)alkyl, (C₁-C₁₀) alkylcarbonyloxy(C₁-C₁₀)alkyl,amino(C₁-C₁₀)alkyl, mono(C₁-C₁₀)alkylamino, di(C₁-C₁₀)alkylamino,arylamino, (C₁-C₁₀)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl or heterocycloalkyl; Y² and Y³ when presenton adjacent carbon atoms together may also form a substituted orunsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure,optionally containing one or two hetero atoms, selected from oxygen,sulfur or nitrogen which comprises: reacting the compound of formula (I)where R¹ represents NHR⁴, wherein R⁴ represents —C(═O)—R^(4b), whereinR^(4b) represents (C₁-C₁₀)alkyl, halo(C₁-C₁₀)alkyl,—C(═O)—(C₁-C₁₀)alkoxy, —C(═O)-aryloxy, —C(═S)—(C₁-C₁₀)alkyl or—C(═S)-aryl; Y¹, Y², Y³, R², R³ and Z are as defined above, with2,4-bis(methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide(Lawesson's reagent).
 82. A process for the preparation of compound offormula (I)

where R¹ represents —NHR⁴, wherein R⁴ represents —C(═S)—SR^(4c) wherein(C₁-C₁₀)alkyl group; R² and R³, which may be the same or different, areeach independently hydrogen, halogen, (C₁-C₁₀)alkyl, halogenated(C₁-C₁₀)alkyl, cyano, nitro, SR^(a), NR^(a), or OR^(a), in which R^(a)is hydrogen, (C₁-C₁₀)alkyl or halogenated (C₁-C₁₀)alkyl;

is a heterocyclic moiety in which

is a 5-membered heterocyclic skeleton, Z represents O, S, ═CH, —CH₂ orNR^(b), where R^(b) is hydrogen or a moiety, which may be substituted orunsubstituted, straight chain or branched, selected from the groupconsisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, (C₃-C₈)cycloalkyl,hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy, (C₁-C₁₀)alkylamino,amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl, aryloxy,(C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀)alkoxycarbonyl andaryloxycarbonyl; Y¹ represents ═O or ═S group and Y² and Y³independently represent hydrogen, halogen, cyano, nitro, formyl,hydroxy, amino, ═O, ═S group or substituted or unsubstituted groupsselected from (C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-₁₀)alkylhydroxy,(C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyl,(C₁-C₁₀)alkoxycarbonyl, arylcarbonyl, carboxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylsulfonyl, (C₁-C₁₀)alkylcarbony(C₁-C₁₀)alkyl,arylcarbonylamino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyloxy(C₁-C₁₀)alkyl,amino(C₁-C₁₀)alkyl, mono(C₁-C₁₀)alkylamino, di(C₁-C₁₀)alkylamino,arylamino, (C₁-C₁₀)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl or heterocycloalkyl; Y² and Y³ when presenton adjacent carbon atoms together may also form a substituted orunsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure,optionally containing one or two hetero atoms, selected from oxygen,sulfur or nitrogen which comprises: reacting the compound of formula (I)where R¹ represents NHR⁴, wherein R⁴ represents hydrogen; Y¹, Y², Y³,R², R³ and Z are as defined above, by reacting with carbondisulfide,with an appropriate alkylhalide and a base selected from Et₃N,diisopropylethylamine, K₂CO₃, NaH or KOt-Bu.
 83. A process for thepreparation of compound of formula (I)

where R¹ represents —NHR⁴, wherein R⁴ represents —C(═S)—OR^(4d), whereinR^(4d) represents (C₁-C₁₀)alkyl, cyclo(C₃-C₈)alkyl, —(C═O)—(C₁-C₁₀)alkylgroup substituted with fluorine, aryl, halo(C₁-C₁₀)alkyl,hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl or (C₂-C₁₀)alkenyl; R²and R³, which may be the same or different, are each independentlyhydrogen, halogen, (C₁-C₁₀)alkyl, halogenated (C₁-C₁₀)alkyl, cyano,nitro, SR^(a), NR^(a), or OR^(a), in which R^(a) is hydrogen,(C₁-C₁₀)alkyl or halogenated (C₁-C₁₀)alkyl;

is a heterocyclic moiety in which

is a 5-membered heterocyclic skeleton, Z represents O, S, ═CH, —CH₂ orNR^(b), where R^(b) is hydrogen or a moiety, which may be substituted orunsubstituted, straight chain or branched, selected from the groupconsisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, (C₃-C₈)cycloalkyl,hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy, (C₁-C₁₀)alkylamino,amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl, aryloxy,(C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀) alkoxycarbonyl andaryloxycarbonyl; Y¹ represents ═O or ═S group and Y² and Y³independently represent hydrogen, halogen, cyano, nitro, formyl,hydroxy, amino, ═O, ═S group or substituted or unsubstituted groupsselected from (C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyl,(C₁-C₁₀)alkoxycarbonyl, arylcarbonyl, carboxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylsulfonyl, (C₁-C₁₀)alkylcarbony(C₁-C₁₀)alkyl,arylcarbonylamino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyloxy(C₁-C₁₀)alkyl,amino(C₁-C₁₀)alkyl, mono(C₁-C₁₀)alkylamino, di(C₁-C₁₀)alkylamino,arylamino, (C₁-C₁₀)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl or heterocycloalkyl; Y² and Y³ when presenton adjacent carbon atoms together may also form a substituted orunsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure,optionally containing one or two hetero atoms, selected from oxygen,sulfur or nitrogen which comprises: (i) converting compound of formula(I) where R¹ represents NHR⁴, wherein R⁴ represents hydrogen atom; Y¹,Y², Y³, R², R³ and Z are as defined above, to a compound of formula (I)where R¹ represents isothiocyanate group and all other symbols are asdefined above, by reacting with thiophosgene and (ii) convertingcompound of formula (I) where R¹ represents isothiocyanate group, to acompound of formula (I) where R¹ represents NHR⁴, wherein R⁴ represents—C(═S)—OR^(4d), wherin R^(4d) represents (C₁-C₁₀)alkyl,cyclo(C₃-C₈)alkyl, —(C═O)—(C₁-C₁₀)alkyl group substituted with fluorine,aryl, halo(C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl or (C₂-C₁₀)alkenyl and all symbols are asdefined above, by reacting with alcohol.
 84. A process for thepreparation of compound of formula (I)

where R¹ represents —NHR⁴, wherein R⁴ represents —C(═S)—N(R′R″), R′represents hydrogen, (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, substituted orunsubstituted aralkyl, heteroaralkyl, hydroxy(C₁-C₁₀)alkyl, R″represents hydrogen or (C₁-C₁₀)alkyl or R′ and R″ together form a 5 or 6membered cyclic structures containing one or two hetero atoms; R² andR³, which may be the same or different, are each independently hydrogen,halogen, (C₁-C₁₀)alkyl, halogenated (C₁-C₁₀)alkyl, cyano, nitro, SR^(a),NR^(a), or OR^(a), in which R^(a) is hydrogen, (C₁-C₁₀)alkyl orhalogenated (C₁-C₁₀)alkyl;

is a heterocyclic moiety in which

is a 5-membered heterocyclic skeleton, Z represents O, S, ═CH, —CH₂ orNR^(b), where R^(b) is hydrogen or a moiety, which may be substituted orunsubstituted, straight chain or branched, selected from the groupconsisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, (C₃-C₈)cycloalkyl,hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy, (C₁-C₁₀)alkylamino,amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl, aryloxy,(C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀)alkoxycarbonyl andaryloxycarbonyl; Y¹ represents ═O or ═S group and Y² and Y³independently represent hydrogen, halogen, cyano, nitro, formyl,hydroxy, amino, ═O, ═S group or substituted or unsubstituted groupsselected from (C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyl,(C₁-C₁₀)alkoxycarbonyl, arylcarbonyl, carboxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylsulfonyl, (C₁-C₁₀)alkylcarbony(C₁-C₁₀)alkyl,arylcarbonylamino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyloxy(C₁-C₁₀)alkyl,amino(C₁-C₁₀)alkyl, mono(C₁-C₁₀)alkylamino, di(C₁-C₁₀)alkylamino,arylamino, (C₁-C₁₀)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl or heterocycloalkyl; Y² and Y³ when presenton adjacent carbon atoms together may also form a substituted orunsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure,optionally containing one or two hetero atoms, selected from oxygen,sulfur or nitrogen which comprises: converting compound of formula (I)where R¹ represents isothiocyante group and all other symbols are asdefined above by passing ammonia gas or by reacting with amine.
 85. Aprocess for the preparation of compound of formula (I),

where Z represents NR^(b) wherein R^(b) represents hydrogen, Y¹represents ‘═O’ group, Y² and Y³ independently represent hydrogen atom;R¹ represents —NHR⁴, wherein R⁴ represents thio(C₁-C₁₀)acyl,—C(═S)-cyclo(C₃-C₈)alkoxy, —C(═S)—(C₁-C₁₀)alkoxy,—C(═S)—(C₂-C₁₀)alkenyloxy, —C(═S)-aryloxy, (C═S)—S—(C₁-C₁₀)alkyl,—(C═S)—NH₂, —(C═S)—NH—(C₁-C₁₀)alkyl, —C(═S)—N—((C₁-C₁₀)alkyl)₂,—C(═S)—NH—(C₂-C₁₀)alkenyl, (C═S)—(C═O)—(C₁-C₁₀)alkoxy,—(C═S)—(C═O)-aryloxy, —C(═S)—O—(C═O)—(C₁-C₁₀)alkyl,C(═S)—C(═S)—(C₁-C₁₀)alkyl, —C(═S)—C(═S)-aryl, —C(═S)-thiomorpholinyl or—(═S)-pyrrolidinyl; R² and R³, which may be the same or different, areeach independently hydrogen, halogen, (C₁-C₁₀)alkyl, halogenated(C₁-C₁₀)alkyl, cyano, nitro, SR^(a), NR^(a), or OR^(a), in which R^(a)is hydrogen, (C₁-C₁₀)alkyl or halogenated (C₁-C₁₀)alkyl; Y¹ represents═O group; Y² and Y³ independently represent hydrogen atom; whichcomprises: reacting the compound of formula (I) where Z representsNR^(b) wherein R^(b) represents substituted or unsubstituted(C₁-C₁₀)alkyl group substituted with hydroxy group at α-position, Y¹represents ‘═O group’, Y² and Y³ independently represent hydrogen atomand all other symbols are as defined above, with a base.
 86. A processfor the preparation of compound of formula (I),

where Z represents NR^(b) wherein R^(b) represents substituted orunsubstituted (C₁-C₁₀)alkyl or aralkyl, Y¹ represents ‘═O group’, Y² andY³ independently represent hydrogen atom; R¹ represents NHR⁴ wherein R⁴represents thio(C₁-C₁₀)acyl, —C(═S)-cyclo(C₃-C₈) alkoxy,—C(═S)—(C₁-C₁₀)alkoxy, —C(═S)—(C₂-C₁₀)alkenyloxy, —C(═S)-aryloxy,(C═S)—S—(C₁-C₁₀)alkyl, —(C═S)—NH₂, —(C═S)—NH—(C₁-C₁₀)alkyl,—C(═S)—N—((C₁-C₁₀)alkyl)₂, —C(═S)—NH—(C₂-C₁₀)alkenyl,(C═S)—(C═O)—(C₁-C₁₀)alkoxy, —(C═S)—(C═O)-aryloxy,—C(═S)—O—(C═O)—(C₁-C₁₀)alkyl, C(═S)—C(═S)—(C₁-C₁₀)alkyl,—C(═S)—C(═S)-aryl, —C(═S)-thiomorpholinyl or —C(═S)-pyrrolidinyl; R² andR³, which may be the same or different, are each independently hydrogen,halogen, (C₁-C₁₀)alkyl, halogenated (C₁-C₁₀)alkyl, cyano, nitro, SR^(a),NR^(a), or OR^(a), in which R^(a) is hydrogen, (C₁-C₁₀)alkyl orhalogenated (C₁-C₁₀)alkyl; which comprises: reacting the compound offormula (I) where Z represents NR^(b) wherein R^(b) represents hydrogenatom; Y¹ represents ‘═O’ group; Y² and Y³ independently representhydrogen atom and all other symbols are as defined above, with a baseand (C₁-C₁₀)alkyl halide.
 87. A process for the preparation of compoundof formula (I),

where R¹ represents NHR⁴ wherein R⁴ represents hydrogen atom, orsubstituted or unsubstituted groups selected from (C₁-C₁₀)alkyl,(C₁-C₁₀)acyl, thio(C₁-C₁₀)acyl, —C(═O)—(C₁-C₁₀)alkoxy,—C(═S)—(C₃-C₈)cycloalkoxy, —C(═O)—(C₂-C₁₀)alkenyloxy,—C(═O)—(C₂-C₁₀)alkenyl, —C(═O)-aryloxy, —C(═S)—(C₁-C₁₀)alkoxy,—C(═S)—(C₂-C₁₀)alkenyloxy, —C(═S)-aryloxy, —C(═O)—C(═O)—(C₁-C₁₀)alkyl,—C(═O)—C(═O)-aryl, —C(═O)—C(═O)—(C₁-C₁₀)alkoxy, —C(═O)—C(═O)-aryloxy,—(C═S)—S—(C₁-C₁₀)alkyl, —(C═S)—NH₂, —(C═S)—NH—(C₁-C₁₀)alkyl,—C(═S)—N—((C₁-C₁₀)alkyl)₂, —C(═S)—NH—(C₂-C₁₀)alkenyl,(C═S)—(C═O)—(C₁-C₁₀)alkoxy, —(C═S)—(C═O)-aryloxy,—C(═S)—O—(C═O)—(C₁-C₁₀)alkyl, C(═S)—C(═S)—(C₁-C₁₀)alkyl,—C(═S)—C(═S)-aryl, thiomorpholinyl-C(═S)— or pyrrolidinyl-C(═S)—; R² andR³, which may be the same or different, are each independently hydrogen,halogen, (C₁-C₁₀)alkyl, halogenated (C₁-C₁₀)alkyl, cyano, nitro, SR^(a),NR^(a), or OR^(a), in which R^(a) is hydrogen, (C₁-C₁₀)alkyl orhalogenated (C₁-C₁₀)alkyl;

is a heterocyclic moiety in which

is a 5-membered heterocyclic skeleton, Z represents O, S, ═CH, —CH₂ orNR^(b), where R^(b) is hydrogen or a moiety, which may be substituted orunsubstituted, straight chain or branched, selected from the groupconsisting of (C₁-C₁₀)alkyl, (C₂-C₁₀)alkenyl, (C₃-C₈)cycloalkyl,hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy, (C₁-C₁₀)alkylamino,amino(C₁-C₁₀)alkyl, (C₁-C₁₀)alkoxy, aryl, aralkyl, aryloxy,(C₁-C₁₀)alkylcarbonyl, arylcarbonyl, (C₁-C₁₀)alkoxycarbonyl andaryloxycarbonyl; Y¹ represents ═O or ═S group and Y² and Y³independently represent hydrogen, halogen, cyano, nitro, formyl,hydroxy, amino, ═O, ═S group or substituted or unsubstituted groupsselected from (C₁-C₁₀)alkyl, hydroxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylhydroxy,(C₁-C₁₀)alkoxy(C₁-C₁₀)alkyl, (C₁-C₁₀)alkylcarbonyl,(C₁-C₁₀)alkoxycarbonyl, arylcarbonyl, carboxy(C₁-C₁₀)alkyl,(C₁-C₁₀)alkylsulfonyl, (C₁-C₁₀)alkylcarbony(C₁-C₁₀)alkyl,arylcarbonylamino(C₁-C₁₀)alkyl, (C₁-C₁₀) alkylcarbonyloxy(C₁-C₁₀)alkyl,amino(C₁-C₁₀)alkyl, mono(C₁-C₁₀)alkylamino, di(C₁-C₁₀)alkylamino,arylamino, (C₁-C₁₀)alkoxy, aryl, aryloxy, aralkyl, heteroaryl,heteroaralkyl, heterocyclyl or heterocycloalkyl; Y² and Y³ when presenton adjacent carbon atoms together may also form a substituted orunsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure,optionally containing one or two hetero atoms selected from oxygen,sulfur or nitrogen, which comprises: (i) reacting the compound offormula (VI),

where all symbols are as defined above, to a compound of formula (VIa)

where all sybols are as defined above, (ii) reacting the compound offormula (VIa), with a compound of formula (IXa)

where R¹ is as defined above, to obtain a compound of formula (I)

where all symbols are as defined above.